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Effect of retinoids on carcinogen-induced mutagenesis in Salmonella tester strains
Abstract:
The ability of retinol (Rol) in altering mutation frequencies induced by 7 carcinogens was studied in Salmonella/microsome assay using 4 tester strains namely TA98, TA100, TA102 and TA1535. The 7 carcinogens used were aflatoxin B1 (AFB), cyclophosphamide (CPP), 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), benz[a]anthracene (BA), 9,10-dimethyl-1,2-benz[a]anthracene (DMBA) and mitomycin C (MMC). As reported previously, Rol significantly reduced the number of His+ revertants induced by AFB. It also reduced mutations induced by CPP or MCA but not that by BP, BA, DMBA or MMC. The abilities of Rol, retinoic acid, retinyl acetate and a known inhibitor for certain P-450 isozymes, 7,8-benzoflavone (BF) in inhibiting mutations caused by AFB and BP were studied and compared. All the 3 retinoids caused significant reduction of AFB-induced His+ revertants in a dose-dependent manner, but there was no effect on BP-induced mutation. BF strongly inhibited both AFB- and BP-induced revertants. The possibility of retinoids in exerting their effects on mutagenesis of precarcinogens by inhibiting only certain forms of cytochrome P-450 enzymes is discussed.
Insights
Retinol (Rol) and other retinoids reduce mutations caused by aflatoxin B1 (AFB) and some carcinogens. However, they do not inhibit mutations induced by benzo[a]pyrene (BP), suggesting specific interactions with carcinogen metabolism.
Area of Science:
- Biochemistry
- Toxicology
- Molecular Biology
Background:
- Retinoids, including retinol (Rol), are known to modulate biological processes.
- Carcinogen-induced mutagenesis is a critical area of toxicological research.
- Cytochrome P-450 enzymes play a key role in the metabolic activation of many carcinogens.
Purpose of the Study:
- To investigate the effect of retinol (Rol) on mutation frequencies induced by seven different carcinogens.
- To compare the inhibitory effects of various retinoids and 7,8-benzoflavone (BF) on mutations induced by aflatoxin B1 (AFB) and benzo[a]pyrene (BP).
- To explore the potential role of specific cytochrome P-450 isozymes in retinoid-mediated modulation of mutagenesis.
Main Methods:
- Salmonella/microsome assay using four tester strains (TA98, TA100, TA102, TA1535).
- Exposure to seven carcinogens: aflatoxin B1 (AFB), cyclophosphamide (CPP), 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), benz[a]anthracene (BA), 9,10-dimethyl-1,2-benz[a]anthracene (DMBA), and mitomycin C (MMC).
- Assessment of inhibition by retinol (Rol), retinoic acid, retinyl acetate, and 7,8-benzoflavone (BF).
Main Results:
- Retinol (Rol) significantly reduced His+ revertants induced by AFB, CPP, and MCA, but not by BP, BA, DMBA, or MMC.
- Retinol (Rol), retinoic acid, and retinyl acetate dose-dependently inhibited AFB-induced mutations but had no effect on BP-induced mutations.
- 7,8-benzoflavone (BF) strongly inhibited mutations induced by both AFB and BP.
Conclusions:
- Retinoids exhibit differential effects on carcinogen-induced mutagenesis, effectively inhibiting some but not others.
- The lack of inhibition on BP-induced mutations suggests retinoids may not affect all cytochrome P-450 isozymes involved in carcinogen metabolism.
- Retinoids may exert their antimutagenic effects by selectively inhibiting specific forms of cytochrome P-450 enzymes.