Suppressive effects of retinoids, carotenoids and antioxidant vitamins on heterocyclic amine-induced umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002).
Effects of retinoids, carotenoids and antioxidant vitamins were studied by mutagen-induced umu C gene expression system in Salmonella typhimurium (TA 1535/pSK 1002). Retinol (vitamin A), retinol acetate and retinoic acid showed remarkable inhibitory activities, whereas retinol palmitate exhibited significant but weak activity for umu C gene expression in tester bacteria induced by 3-amino-3,4-dimethyl-5H-pyrido[4.3-b]indol (Trp-P-1) in the presence of hepatic metabolizing enzymes (S9 mixture). Carotenoids having provitamin A activity (beta-carotene and canthaxanthin) exhibited moderate suppressive effects on the same experimental system. The ranks of suppressive activities were retinol > retinol acetate > retinoic acid > canthaxanthin > beta-carotene > retinol palmitate and their doses for inhibition by 50% (ID50) were estimated to be 1.2 x 10(-7), 3.0 x 10(-7), 5.4 x 10(-7), 1.5 x 10(-6), 4.0 x 10(-5) and 6.0 x 10(-5) M, respectively. However, they did not cause significant inhibition on umu C gene expression induced by direct-acting mutagen (adriamycin or mitomycin C) in the absence of S9 mixture. Inhibition of umu gene expression appears to be due to inhibition of P450-mediated metabolic activation of the heterocyclic amine Trp-P-1. Ascorbic acid (vitamin C) showed weak but significant suppressive activity at high-dose concentrations (3 x 10(-6) - 10(-4)M). However, alpha-tocopherol did not exhibit significant suppression at all dose concentrations. The significance of the experimental results is discussed from the viewpoint of the chemoprevention against genotoxicity associated with carcinogenesis.
Okai
Y
Y
Division of Food and Nutrition, Osaka Kun-ei Women's College, Japan.
Higashi-Okai
K
K
Nakamura
S
S
Yano
Y
Y
Otani
S
S
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001426:Bacterial Proteins / Q000187:drug effects* / Q000235:genetics; D002243:Carbolines / Q000633:toxicity; D002338:Carotenoids / Q000494:pharmacology*; D004259:DNA-Directed DNA Polymerase; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins; D015870:Gene Expression / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009153:Mutagens / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D014815:Vitamins / Q000494:pharmacology*
D016587:Antimutagenic Agents; D000975:Antioxidants; D001426:Bacterial Proteins; D002243:Carbolines; D029968:Escherichia coli Proteins; D006571:Heterocyclic Compounds; D009153:Mutagens; D012176:Retinoids; D014815:Vitamins; D002338:Carotenoids; C078202:UmuC protein, E coli; D004259:DNA-Directed DNA Polymerase; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole