CHROMOSOMAL-ABERRATIONS AND SISTER-CHROMATID EXCHANGES INDUCED BY N-NITROSO-2-ACETYLAMINOFLUORENE AND THEIR MODIFICATIONS BY ARSENITE AND SELENITE IN CHINESE-HAMSTER OVARY CELLS

The frequencies of chromosomal aberrations (CA) and sister-chromatid exchanges (SCE) in Chinese hamster cells were significantly increased by the direct-acting mutagen N-nitroso-2-acetylaminofluorene (N-NO-AAF) at the concentration of 0.1 mM. N-NO-AAF was prepared by nitrosation of the proto-hepatocarcinogen 2-acetylaminofluorene. The induced CA, which included chromatid breaks, chromatid exchanges, chromosome breaks, and chromosome ring formation were significantly potentiated by the presence of sodium arsenite (10-mu-M), but not by hydroxyurea (20 mM) or cytosine arabinoside (25-mu-M). On the other hand, the clastogenic effect of N-NO-AAF was effectively inhibited by sodium selenite (100-mu-M). Arsenite (10-mu-M) was shown to be moderately active in CA induction which was partially blocked by the presence of selenite (10 nM). N-Nitroso compounds such as N-nitroso-N-methylurea, N-nitroso-N-ethylurea and N-methyl-N'-nitro-N-nitrosoguanidine were equally or more active in the induction of CA and SCE in CHO cells when compared with N-NO-AAF. The cell cycle was significantly delayed by the intervention of N-NO-AAF.