Influence of retinol on carcinogen-induced sister chromatid exchanges and chromosome aberrations in V79 cells.

Abstract

The influence of retinol (Rol) on sister chromatid exchanges (SCE) in V79 cells induced by six indirect and two direct carcinogens, and on chromosome aberration (CA) in V79 cells induced by four indirect carcinogens were studied. The indirect carcinogens used were aflatoxin B1 (AFB), cyclophosphamide (CPP), benzo(a)-anthracene (BA), benzo(a)pyrene (BP), 9,10-dimethyl-1,2-benz(a)anthracene (DMBA), and 3-methylcholanthrene (MCA). The two direct carcinogens were ethyl methane sulfonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rol effectively inhibited SCE and CA induced by AFB and CPP in a dose-dependent manner, but it had no effect on SCE induced by BA, BP, DMBA, MCA, EMS, and MMNG. To the contrary, Rol had an enhancing effect on CA induced by BP and DMBA. Altering the concentration of the metabolic activation system-S9 mix had a significant effect on inhibition of AFB and CPP induced SCE by Rol. A high ratio of Rol/S9 mix resulted in a maximum effect of inhibition of SCE frequencies. Using low concentrations of S9 mix and various doses of Rol close to physiological levels (2 micrograms/ml and below) demonstrated a dose-dependent inhibition of AFB- and CPP-induced SCE. The possibility that Rol exerts its anticarcinogenic effects by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of precarcinogens, such as AFB and CPP but not those enzymes required by BA, BP, DMBA, and MCA, is discussed.