Strong anti-mutagenic activity of the novel lipophilic antioxidant 1-O-hexyl-2,3,5-trimethylhydroquinone against heterocyclic amine-induced mutagenesis in the Ames assay and its effect on metabolic activation of 2-amino-6-methyldipyrido[1,2-a:3',2'-d] imidazole (Glu-p-1).

Authors:
M Hirose
M Hirose
Albert-Ludwigs-Universit├Ąt
Germany
E Ito
E Ito
Kagawa School of Pharmaceutical Sciences
Japan
T Miki
T Miki
Kagawa University
Japan

Carcinogenesis 1995 Sep;16(9):2227-32

First Department of Pathology, Nagoya City University, Medical School, Japan.

Antimutagenic effects of a novel lipophilic antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), and other known antioxidants against heterocyclic amine- or other mutagen-induced mutagenesis were examined in the Ames assay using Salmonella strain TA 98 to access the chemo-preventive effects of antioxidants on heterocyclic amine-induced carcinogenesis. Further the mechanisms of inhibition by HTHQ were accessed. HTHQ was shown to potently inhibit mutagenesis induced by all of 8 different heterocyclic amines at rates between 100% and 63% in the presence of S9 mix. When the protection of HTHQ against 2-amino-6- methyldipyrido[1,2-alpha:3',2'-d]imidazole (Glu-P-1)-induced mutagenesis was compared with known antioxidants t-butylhydroquinone, propyl gallate, BHA, BHT and alpha-tocopherol, HTHQ showed the greatest effect. Among hexyl, butyl, ethyl and methyl derivatives of 1-O-alkyl-2,3,5-trimethylhydroquinone, HTHQ was the most effective in inhibiting Glu-P-1-, 3-amino-1-methyl-5-H-pyrido[4,3-b]indole (Trp-P-2)- or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced mutagenesis. On the other hand, HTHQ did not inhibit mutagenic activity induced by other mutagens such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) and benzo[a]pyrene. HTHQ weakly inhibited that due to direct mutagen 2-nitro derivative of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) only in the presence of S9 mix. No such influence on a 2-nitro derivative of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mutagenesis, was observed with or without the S9 mix. HTHQ slightly inhibited mutagenesis induced by activated Glu-P-1, a direct acting proximate metabolite of Glu-P-1, in the absence of the S9 mix. HPLC analysis revealed activated Glu-P-1 to be formed by incubating Glu-P-1 with the S9 mix, but this was considerably decreased by the addition of HTHQ. These results indicate that HTHQ is a powerful antimutagenic compound and specifically acts against heterocyclic amines. Its antimutagenic activity appeared to exert by both inhibiting metabolic activation of heterocyclic amines and action on activated N-hydroxy species.
September 1995
5 Reads

Publication Analysis

Top Keywords

heterocyclic amines
12
hthq
11
ames assay
8
heterocyclic amine-induced
8
metabolic activation
8
2-nitro derivative
8
mutagenesis induced
8
antioxidant 1-o-hexyl-235-trimethylhydroquinone
8
antioxidants heterocyclic
8
presence mix
8
activated glu-p-1
8
lipophilic antioxidant
8
novel lipophilic
8
mutagenesis
7
heterocyclic
6
glu-p-1
5
mix
5
glu-p-1 mix
4
3-amino-1-methyl-5-h-pyrido[43-b]indole trp-p-2-
4
methyl derivatives
4

Similar Publications

Phenolics: blocking agents for heterocyclic amine-induced carcinogenesis.

Food Chem Toxicol 1999 Sep-Oct;37(9-10):985-92

First Department of Pathology, Nagoya City University, Medical School, Nagoya, Japan.

Chemopreventive effects of synthetic and naturally occurring antioxidants on heterocyclic amine (HCA)-induced rat carcinogenesis and mechanisms of inhibition were assessed. In a medium-term liver bioassay, combined treatment with 0.03% 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and synthetic antioxidants such as 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), butylated hydroxyanisole (BHA), butylated hydroxutoluene (BHT), tert-butylhydroquinone (TBHQ) or propyl gallate, each at a dose of 0. Read More

View Article
November 1999

Prevention by antioxidants of heterocyclic amine-induced carcinogenesis in a rat medium-term liver bioassay: results of extended and combination treatment experiments.

Eur J Cancer Prev 1998 Feb;7(1):61-7

First Department of Pathology, Nagoya City University, Medical School, Japan.

The effects of 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) and other antioxidants on heterocyclic amine (HCA)-induced rat hepatocarcinogenesis were examined in a medium-term liver bioassay. In one study the experimental period was extended for up to 28 weeks to confirm the inhibition of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1)-induction of glutathione-S-transferase placental form (GST-P) positive foci detected earlier in an 8-week experiment. Six-week-old male F344 rats were given a single i. Read More

View Article
February 1998

Prevention by synthetic phenolic antioxidants of 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)- or activated MeIQx-induced mutagenesis and MeIQx-induced rat hepatocarcinogenesis, and role of antioxidant activity in the prevention of carcinogenesis.

Eur J Cancer Prev 1998 Jun;7(3):233-41

First Department of Pathology, Nagoya City University, Medical School, Japan.

Effects of synthetic phenolic antioxidants 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butylhydroquinone (TBHQ) and propyl gallate (PG) on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)- or activated MeIQx-induced mutagenesis and rat hepatocarcinogenesis were compared, and the association between antioxidative activity and inhibition of carcinogenesis was examined. When the antimutagenic activity of five antioxidants against MeIQx- or activated MeIQx-induced mutagenesis was compared in the Ames assay using the Salmonella strain TA 98, HTHQ showed the greatest effect, followed by BHA, BHT, PG and TBHQ, in that order. In a rat hepatocarcinogenesis study, 6-week-old male F344 rats were given a single i. Read More

View Article
June 1998

Inhibitory effects of beer on heterocyclic amine-induced mutagenesis and PhIP-induced aberrant crypt foci in rat colon.

Mutat Res 2004 Apr;559(1-2):177-87

Central Laboratories for Key Technology, Kirin Brewery Co. Ltd., 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.

Anti-mutagenic and anti-carcinogenic effects of beer on heterocyclic amine (HCA)-induced carcinogenesis were studied in vitro and in vivo. Four commercial beers (two pilsner-type, black, and stout) showed inhibitory effects against five HCAs, 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), in the Ames assay using Salmonella typhimurium TA98 in the presence of rat S9 mix. The inhibitory effects of dark-colored beers (stout and black beer) were greater than those of pilsner-type beers. Read More

View Article
April 2004