Publications by authors named "Keqi Li"

14 Publications

  • Page 1 of 1

Discovery of Genomic Regions and Candidate Genes Controlling Root Development Using a Recombinant Inbred Line Population in Rapeseed ( L.).

Int J Mol Sci 2022 Apr 26;23(9). Epub 2022 Apr 26.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences/Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture and Rural Affairs, Wuhan 430062, China.

Marker-assisted selection enables breeders to quickly select excellent root architectural variations, which play an essential role in plant productivity. Here, ten root-related and shoot biomass traits of a new F recombinant inbred line (RIL) population were investigated under hydroponics and resulted in high heritabilities from 0.61 to 0.83. A high-density linkage map of the RIL population was constructed using a 50k Illumina single nucleotide polymorphism (SNP) array. A total of 86 quantitative trait loci (QTLs) explaining 4.16-14.1% of the phenotypic variances were detected and integrated into eight stable QTL clusters, which were repeatedly detected in different experiments. The codominant markers were developed to be tightly linked with three major QTL clusters, , , and , which controlled both root-related and shoot biomass traits and had phenotypic contributions greater than 10%. Among these, , renamed , was further fine-mapped to a 129-kb interval with 19 annotated genes in the reference genome. By integrating the results of real-time PCR and comparative sequencing, five genes with expression differences and/or amino acid differences were identified as important candidate genes for . Our findings laid the foundation for revealing the molecular mechanism of root development and developed valuable markers for root genetic improvement in rapeseed.
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http://dx.doi.org/10.3390/ijms23094781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102059PMC
April 2022

Genetic Dissection of Mature Root Characteristics by Genome-Wide Association Studies in Rapeseed ( L.).

Plants (Basel) 2021 Nov 24;10(12). Epub 2021 Nov 24.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Ministry of Agriculture, Wuhan 430062, China.

Roots are complicated quantitative characteristics that play an essential role in absorbing water and nutrients. To uncover the genetic variations for root-related traits in rapeseed, twelve mature root traits of a association panel were investigated in the field within three environments. All traits showed significant phenotypic variation among genotypes, with heritabilities ranging from 55.18% to 79.68%. Genome-wide association studies (GWAS) using 20,131 SNPs discovered 172 marker-trait associations, including 103 significant SNPs (-log10 () > 4.30) that explained 5.24-20.31% of the phenotypic variance. With the linkage disequilibrium r > 0.2, these significant associations were binned into 40 quantitative trait loci (QTL) clusters. Among them, 14 important QTL clusters were discovered in two environments and/or with phenotypic contributions greater than 10%. By analyzing the genomic regions within 100 kb upstream and downstream of the peak SNPs within the 14 loci, 334 annotated genes were found. Among these, 32 genes were potentially associated with root development according to their expression analysis. Furthermore, the protein interaction network using the 334 annotated genes gave nine genes involved in a substantial number of interactions, including a key gene associated with root development, This research provides the groundwork for deciphering ' genetic variations and improving its root system architecture.
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http://dx.doi.org/10.3390/plants10122569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705616PMC
November 2021

Development and validation of the SARICA score to predict survival after return of spontaneous circulation in out of hospital cardiac arrest using an interpretable machine learning framework.

Resuscitation 2022 01 26;170:126-133. Epub 2021 Nov 26.

Pre-hospital and Emergency Research Centre, Duke-NUS Medical School, Singapore; Department of Emergency Medicine, Singapore General Hospital, Singapore. Electronic address:

Background: Accurate and timely prognostication of patients with out-of-hospital cardiac arrest (OHCA) who achieved the return of spontaneous circulation (ROSC) is crucial in clinical decision-making, resource allocation, and communications with next-of-kins. We aimed to develop the Survival After ROSC in Cardiac Arrest (SARICA), a practical clinical decision tool to predict survival in OHCA patients who attained ROSC.

Methods: We utilized real-world Singapore data from the population-based Pan-Asian Resuscitation Outcomes Study between 2010-2018. We excluded patients without ROSC. The dataset was segmented into training (60%), validation (20%) and testing (20%) cohorts. The primary endpoint was survival (to 30-days or hospital discharge). AutoScore, an interpretable machine-learning based clinical score generation algorithm, was used to develop SARICA. Candidate factors were chosen based on objective demographic and clinical factors commonly available at the time of admission. Performance of SARICA was evaluated based on receiver-operating curve (ROC) analyses.

Results: 5970 patients were included, of which 855 (14.3%) survived. A three-variable model was determined to be most parsimonious. Prehospital ROSC, age, and initial heart rhythm were identified for inclusion via random forest selection. Finally, SARICA consisted of these 3 variables and ranged from 0 to 10 points, achieving an area under the ROC (AUC) of 0.87 (95% confidence interval: 0.84-0.90) within the testing cohort.

Conclusion: We developed and internally validated the SARICA score to accurately predict survival of OHCA patients with ROSC at the time of admission. SARICA is clinically practical and developed using an interpretable machine-learning framework. SARICA has unknown generalizability pending external validation studies.
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http://dx.doi.org/10.1016/j.resuscitation.2021.11.029DOI Listing
January 2022

Genome-wide association study and transcriptome analysis reveal key genes affecting root growth dynamics in rapeseed.

Biotechnol Biofuels 2021 Sep 10;14(1):178. Epub 2021 Sep 10.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences/Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Wuhan, 430062, China.

Background: In terms of global demand, rapeseed is the third-largest oilseed crop after soybeans and palm, which produces vegetable oil for human consumption and biofuel for industrial production. Roots are vital organs for plant to absorb water and attain mineral nutrients, thus they are of great importance to plant productivity. However, the genetic mechanisms regulating root development in rapeseed remain unclear. In the present study, seven root-related traits and shoot biomass traits in 280 Brassica napus accessions at five continuous vegetative stages were measured to establish the genetic basis of root growth in rapeseed.

Results: The persistent and stage-specific genetic mechanisms were revealed by root dynamic analysis. Sixteen persistent and 32 stage-specific quantitative trait loci (QTL) clusters were identified through genome-wide association study (GWAS). Root samples with contrasting (slow and fast) growth rates throughout the investigated stages and those with obvious stage-specific changes in growth rates were subjected to transcriptome analysis. A total of 367 differentially expressed genes (DEGs) with persistent differential expressions throughout root development were identified, and these DEGs were significantly enriched in GO terms, such as energy metabolism and response to biotic or abiotic stress. Totally, 485 stage-specific DEGs with different expressions at specific stage were identified, and these DEGs were enriched in GO terms, such as nitrogen metabolism. Four candidate genes were identified as key persistent genetic factors and eight as stage-specific ones by integrating GWAS, weighted gene co-expression network analysis (WGCNA), and differential expression analysis. These candidate genes were speculated to regulate root system development, and they were less than 100 kb away from peak SNPs of QTL clusters. The homologs of three genes (BnaA03g52990D, BnaA06g37280D, and BnaA09g07580D) out of 12 candidate genes have been reported to regulate root development in previous studies.

Conclusions: Sixteen QTL clusters and four candidate genes controlling persistently root development, and 32 QTL clusters and eight candidate genes stage-specifically regulating root growth in rapeseed were detected in this study. Our results provide new insights into the temporal genetic mechanisms of root growth by identifying key candidate QTL/genes in rapeseed.
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http://dx.doi.org/10.1186/s13068-021-02032-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431925PMC
September 2021

Evolution of the Brassicaceae-specific MS5-Like family and neofunctionalization of the novel MALE STERILITY 5 gene essential for male fertility in Brassica napus.

New Phytol 2021 02 23;229(4):2339-2356. Epub 2020 Nov 23.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences/Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Wuhan, 430062, China.

New genes (or lineage-specific genes) can facilitate functional innovations. MALE STERILITY 5 (MS5) in Brassica napus is a fertility-related new gene, which has two wild-type alleles (BnMS5 and BnMS5 ) and two mutant alleles (BnMS5 and BnMS5 ) that could induce male sterility. Here, we studied the history and functional evolution of MS5 homologs in plants by phylogenetic analysis and molecular genetic experiments. We identified 727 MS5 homologs and found that they define a Brassicaceae-specific gene family that has expanded partly via multiple tandem gene duplications and also probably transpositions. The MS5 in B. napus is inherited from a basic diploid ancestor of B. rapa. Molecular genetic experiments indicate that BnMS5 and BnMS5 are functionally distinct in B. napus and that BnMS5 can inhibit BnMS5 in B. napus in a dosage-dependent manner. The BnMS5 protein can move in coordination with meiotic telomeres and interact with the nuclear envelope protein SUN1, with a possible crucial role in meiotic chromosome behavior. In summary, BnMS5 belongs to a Brassicaceae-specific new gene family, and has gained a novel function that is essential for male fertility in B. napus through neofunctionalization that has likely occurred since the origin of B. rapa.
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http://dx.doi.org/10.1111/nph.17053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894334PMC
February 2021

Rolling Circle Amplification (RCA)-Mediated Genome-Wide ihpRNAi Mutant Library Construction in .

Int J Mol Sci 2020 Sep 30;21(19). Epub 2020 Sep 30.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Wuhan 430062, China.

With the successful completion of genomic sequencing for , identification of novel genes, determination of functions performed by genes, and exploring the molecular mechanisms underlying important agronomic traits were challenged. Mutagenesis-based functional genomics techniques including chemical, physical, and insertional mutagenesis have been used successfully in the functional characterization of genes. However, these techniques had their disadvantages and inherent limitations for allopolyploid , which contained a large number of homologous and redundant genes. Long intron-spliced hairpin RNA (ihpRNA) constructs which contained inverted repeats of the target gene separated by an intron, had been shown to be very effective in triggering RNAi in plants. In the present study, the genome-wide long ihpRNA library of was constructed with the rolling circle amplification (RCA)-mediated technology. Using the phytoene desaturase () gene as a target control, it was shown that the RCA-mediated long ihpRNA construct was significantly effective in triggering gene silence in . Subsequently, the resultant long ihpRNA library was transformed into to produce corresponding RNAi mutants. Among the obtained transgenic ihpRNA population of , five ihpRNA lines with observable mutant phenotypes were acquired including alterations in the floral model and the stamen development. The target genes could be quickly identified using specific primers. These results showed that the RCA-mediated ihpRNA construction method was effective for the genome-wide long ihpRNA library of therefore providing a platform for study of functional genomics in allopolyploid .
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http://dx.doi.org/10.3390/ijms21197243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582411PMC
September 2020

Expression and subcellular analyses of CCR8a/b genes with the identification of response to SGIV viral infect in orange-spotted grouper (Epinephelus coioides).

Fish Shellfish Immunol 2020 Nov 24;106:628-639. Epub 2020 Aug 24.

College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, People's Republic of China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, People's Republic of China; Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, People's Republic of China. Electronic address:

Chemokine receptors are a superfamily of seven transmembrane domain G-coupled receptors, and they play important roles in immune surveillance, inflammation, and development. Recently, nine CC chemokine receptors (CCRs) were identified and cloned from orange-spotted grouper (Epinephelus coioides) and annotated by phylogenetic and syntenic analyses. We detected mRNA transcripts for CCRs in healthy tissues of E. coioides, and CCR genes were highly expressed in the immune-relevant tissues. Analysis of gene expression after Singapore grouper iridovirus (SGIV) infection indicated that CCR genes are regulated in a gene-specific manner. CCR8a and CCR8b were significantly upregulated in the spleen and liver of resistant fish, indicating potential roles in immunity against the pathogen. Fluorescence microscopy revealed that CCR8a and CCR8b were expressed predominantly in the cytoplasm. Overexpression of CCR8a and CCR8b in grouper cells significantly inhibited the replication of SGIV, demonstrating that they delayed the occurrence of cytopathic effects induced by SGIV infection and inhibited viral gene transcription. CCR8a and CCR8b overexpression also significantly increased the expression of interferon (IFN)-related cytokines and activated IFN response element and IFN promoter activities. These results demonstrated that CCR8a and CCR8b might have an antiviral function against SGIV infect.
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http://dx.doi.org/10.1016/j.fsi.2020.08.030DOI Listing
November 2020

Nuclear Envelope-Associated Chromosome Dynamics during Meiotic Prophase I.

Front Cell Dev Biol 2017 9;5:121. Epub 2018 Jan 9.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Wuhan, China.

Chromosome dynamics during meiotic prophase I are associated with a series of major events such as chromosomal reorganization and condensation, pairing/synapsis and recombination of the homologs, and chromosome movements at the nuclear envelope (NE). The NE is the barrier separating the nucleus from the cytoplasm and thus plays a central role in NE-associated chromosomal movements during meiosis. Previous studies have shown in various species that NE-linked chromosome dynamics are actually driven by the cytoskeleton. The linker of nucleoskeleton and cytoskeleton (LINC) complexes are important constituents of the NE that facilitate in the transfer of cytoskeletal forces across the NE to individual chromosomes. The LINCs consist of the inner and outer NE proteins Sad1/UNC-84 (SUN), and Klarsicht/Anc-1/Syne (KASH) domain proteins. Meiosis-specific adaptations of the LINC components and unique modifications of the NE are required during chromosomal movements. Nonetheless, the actual role of the NE in chromosomic dynamic movements in plants remains elusive. This review summarizes the findings of recent studies on meiosis-specific constituents and modifications of the NE and corresponding nucleoplasmic/cytoplasmic adaptors being involved in NE-associated movement of meiotic chromosomes, as well as describes the potential molecular network of transferring cytoplasm-derived forces into meiotic chromosomes in model organisms. It helps to gain a better understanding of the NE-associated meiotic chromosomal movements in plants.
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http://dx.doi.org/10.3389/fcell.2017.00121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767173PMC
January 2018

Identification and Analysis of : A Gene That Affects Double-Strand Break (DSB) Repair during Meiosis I in Microsporocytes.

Front Plant Sci 2016 4;7:1966. Epub 2017 Jan 4.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences Wuhan, China.

Here, we report the identification of the -specific gene , which is responsible for male sterility in . The gene is highly expressed in the microsporocyte and encodes a protein that localizes to the nucleus. Light microscopy analyses have demonstrated that the gene affects microsporocyte meiosis in the thermosensitive genic male sterility line TE5A. Sequence comparisons and genetic complementation revealed a C-to-T transition in , encoding a Leu-to-Phe (L281F) substitution and causing abnormal male meiosis in TE5A. These findings suggest arrested meiotic chromosome dynamics at pachytene. Furthermore, immunofluorescence analyses showed that double-strand break (DSB) formation and axial elements were normal but that DSB repair and spindle behavior were aberrant in TE5A meiocytes. Collectively, our results indicate that likely encodes a protein required for chromosomal DSB repair at early stages of meiosis in .
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http://dx.doi.org/10.3389/fpls.2016.01966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209369PMC
January 2017

Aberrant Meiotic Prophase I Leads to Genic Male Sterility in the Novel TE5A Mutant of Brassica napus.

Sci Rep 2016 Sep 27;6:33955. Epub 2016 Sep 27.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences/Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Wuhan 430062, China.

Genic male sterility (GMS) has already been extensively utilized for hybrid rapeseed production. TE5A is a novel thermo-sensitive dominant GMS line in Brassica napus, however, its mechanisms of GMS remain largely unclear. Histological and Transmission electron microscopy (TEM) analyses of anthers showed that the male gamete development of TE5A was arrested at meiosis prophase I. EdU uptake of S-phase meiocytes revealed that the TE5A mutant could accomplish DNA replication, however, chromosomal and fluorescence in situ hybridization (FISH) analyses of TE5A showed that homologous chromosomes could not pair, synapse, condense and form bivalents. We then analyzed the transcriptome differences between young floral buds of sterile plants and its near-isogenic fertile plants through RNA-Seq. A total of 3,841 differentially expressed genes (DEGs) were obtained, some of which were associated with homologous chromosome behavior and cell cycle control during meiosis. Dynamic expression changes of selected candidate DEGs were then analyzed at different anther developmental stages. The present study not only demonstrated that the TE5A mutant had defects in meiotic prophase I via detailed cytological analysis, but also provided a global insight into GMS-associated DEGs and elucidated the mechanisms of GMS in TE5A through RNA-Seq.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037387PMC
http://dx.doi.org/10.1038/srep33955DOI Listing
September 2016

Benzene exposure measurement in shoe and glue manufacturing: a study to validate biomarkers.

Appl Occup Environ Hyg 2003 Dec;18(12):988-98

New York University School of Medicine, Tuxedo, New York, USA.

This article reports an extensive program to monitor individual personal exposures of subjects recruited for a study conducted in a Chinese occupational population to determine whether selected biological markers of exposure to benzene are reliable and sensitive enough to detect low-level benzene exposure in people. The monitoring program reported here was to assure an appropriate range of exposure for subject selection as well as to provide data for the exposure response assessment. The overall study resulted in correlation of the measured exposures with the measured concentrations of two minor urinary benzene metabolites, trans,trans-muconic acid and S-phenylmercapturic acid. The study design and evaluation of biological end points are presented in separate publications. Recruitment of 130 exposed subjects was based on personal exposure measurements collected with passive organic vapor monitors at weekly intervals for 3 to 4 weeks prior to collection of biological samples. Two monitors, side by side, were used for all of the personal monitoring in the first year of the study and about 10 percent of subsequent monitoring. One of each pair was analyzed immediately in Beijing at the Institute of Occupational Medicine, and the other was shipped to the United States and analyzed at the New York University Institute of Environmental Medicine. Exposure concentrations measured over 4-5 weeks were reasonably stable with average coefficients of variation of 0.58, 0.59, and 0.46 for benzene, toluene, and xylene, respectively. Benzene exposure averaged 10 +/- 13 ppm benzene with a median of 3.8 ppm for the recruited exposed workers. Excellent correlation was obtained between samples analyzed for benzene at the two laboratories. The extensive effort to document exposures was important to the exposure-response relationship demonstrated in the full study, which concluded that S-phenylmercapturic acid appears to be a good biomarker for detecting and evaluating benzene exposure at concentrations less than 0.25 ppm.
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http://dx.doi.org/10.1080/714044188DOI Listing
December 2003

Validation and evaluation of biomarkers in workers exposed to benzene in China.

Res Rep Health Eff Inst 2003 Jun(115):1-72; discussion 73-87

Nelson Institute of Environmental Medicine, New York University School of Medicine. 57 Old Forge Rd, Tuxedo NY 10987, USA.

This study was conducted to validate biomarkers for early detection of benzene exposure and effect in 2 phases. The main purpose of phase 1 was to determine whether these biomarkers could reliably detect differences between workers with high exposure levels and unexposed subjects, which is the minimal screening criterion for a biomarker assay. Phase 2 of the study mainly focused on evaluating the exposure-response relation, confounding factors, and sensitivities of biomarkers for low benzene exposures. The Chinese occupational population studied had a broad range of benzene exposures. On the day of biological sample collection, exposures ranged from 0.06 to 122 ppm with a median exposure of 3.2 ppm. The median of the 4-week mean benzene exposures was 3.8 ppm, and the median lifetime cumulative exposure was 51.1 ppm-years. Compared with benzene levels in collected samples, toluene levels were relatively high, with a median of 12.6 ppm (mean, 26.3 ppm), but xylene levels were low, with a median of 0.30 ppm (mean, 0.40 ppm). The biomarkers evaluated were urinary metabolites S-phenylmercapturic acid (S-PMA*), trans,trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), and phenol; albumin adducts of benzene oxide and 1,4-benzoquinone (BO-Alb and 1,4-BQ-Alb, respectively) in blood; blood cell counts; and chromosomal aberrations. Blood cell counts in this population, including red blood cells (RBCs), white blood cells (WBCs), and neutrophils, decreased significantly with increased exposures but remained in normal ranges. Chromosomal aberration data showed significant increases of chromatid breaks and total chromosomal aberrations in exposed subjects compared with unexposed subjects. Among the urinary metabolites, the levels of S-PMA and t,t-MA were significantly elevated after benzene exposures. Both markers showed significant exposure-response trends even over the exposure range from 0 to 1 ppm. However, HQ, CAT, and phenol showed significant increases only for benzene exposure levels above 5 ppm. Multiple regression analyses of these urinary metabolites on benzene exposure indicated that toluene exposure, smoking status, and cotinine levels had no significant effects on urinary metabolite levels. A time-course study estimated the half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol to be 12.8, 13.7, 12.7, 15.0, and 16.3 hours, respectively. Both BO-Alb and 1,4-BQ-Alb showed strong exposure-response associations with benzene. Regression analyses showed that after adjustment for potential confounding by smoking, there was still a strong association between benzene exposure and these markers. Furthermore, the analyses for correlations among biomarkers revealed that the urinary metabolites correlated substantially with each other. The albumin adducts also correlated well with the urinary biomarkers, especially with S-PMA. BO-Alb and 1,4-BQ adducts also correlated well with each other (r = 0.74). For benzene exposure monitoring, both S-PMA and t,t-MA were judged to be good and sensitive markers, which detected benzene exposures at around 0.1 ppm and 1 ppm, respectively. But S-PMA was clearly superior to t,t-MA as a biomarker for low levels of benzene exposure.
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June 2003

Hematological changes among Chinese workers with a broad range of benzene exposures.

Am J Ind Med 2002 Oct;42(4):275-85

Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.

Background: Depression of peripheral blood cells is a well-known indicator of benzene hematotoxicity. Previous studies of its effects on specific types of blood cells have yielded inconsistent results. We examine hematological findings and their possible relations with exposure markers validated in a recent biomarker project conducted in Tianjin, China.

Methods: Personal benzene exposures were sampled with 3-M organic vapor monitors, and analyzed by gas chromatography. The peripheral blood cells were counted by a cell counter. The WBC differential was manually counted on a total of 900 cells by a US commercial laboratory.

Results: A total of 130 exposed workers and 51 age- and gender-matched unexposed subjects were recruited in this study. Benzene exposure levels monitored on the day of biological sample collection for exposed workers ranged from 0.06 to 122 ppm. Their 4-week average and cumulative benzene exposure levels were 0.08-54.5 ppm and 6.1-623.2 ppm-years, respectively. Significant decreases of red blood cells (RBC), white blood cells (WBC), and neutrophils were observed and correlated with both personal benzene exposures and levels of urinary metabolites (S-phenylmercapuric acid and t,t-muconic acid) and albumin adducts of benzene oxide and 1,4-benzeoquinone.

Conclusions: The depressions in RBC, WBC, and neutrophils observed in this study are not only exposure dependent, but also significantly different in the lowest exposed group (at or below 0.25 ppm) compared with unexposed subjects. The results of the present study appear to suggest that lymphocytes may not be more sensitive to chronic benzene exposure than neutrophils.
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http://dx.doi.org/10.1002/ajim.10121DOI Listing
October 2002

Albumin adducts of benzene oxide and 1,4-benzoquinone as measures of human benzene metabolism.

Cancer Res 2002 Mar;62(5):1330-7

School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599-7400, USA.

Albumin adducts of benzene oxide (BO-Alb) and 1,4-benzoquinone (1,4-BQ-Alb) were investigated among 134 workers exposed to benzene and 51 unexposed controls in Tianjin, China. Concentrations of both adducts increased with benzene exposure [range = 0.07-46.6 parts/million (ppm); median = 3.55 ppm] and with urinary cotinine. Adduct levels were less than proportional to benzene exposure, suggesting saturable CYP 2E1 metabolism of benzene. Because the transition from linear to saturable metabolism began at approximately 1 ppm, the common assumption of linear kinetics at much higher benzene exposures could lead to substantial underestimation of leukemia risks. Adduct levels were generally lower in older workers, indicating that CYP 2E1 metabolism diminished with age, at approximately 2%/year of life. The ratio of 1,4-BQ-Alb:BO-Alb decreased with age and coexposure to toluene, and increased with alcohol consumption. This indicates that factors affecting CYP 2E1 metabolism exerted a greater role on production of 1,4-BQ than BO, presumably because of the second oxidation step from phenol to hydroquinone. The adduct ratio was also positively associated with urinary cotinine, suggesting that both benzene and hydroquinone from cigarette smoke affected adduct levels. Results of a limited time course study of 11 subjects indicated moderate chemical instability of 1,4-BQ-Alb (half life = 13.5 days compared with 21 days for normal Alb turnover), whereas no evidence of instability of BO-Alb was observed. This study illustrates that Alb adducts can be used to investigate the dispositions of reactive metabolites of procarcinogens in humans, provided that exposures are adequately characterized in the month preceding blood collection.
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March 2002
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