INHIBITORY ACTIVITY OF CIGARETTE-SMOKE CONDENSATE ON THE MUTAGENICITYOF HETEROCYCLIC AMINES

Cigarette-smoke condensate (CSC) is a complex mixture containing over 3800 identified chemicals including nicotine, water, mutagens, antimut agens, cytotoxins and inert chemicals. Although CSC is mutagenic in th e Ames test, its effect on the activity of other mutagens has not been characterized. Using the Ames Salmonella bacterial mutagenesis assay, we found CSC exerts a significant inhibitory effect on mutagens requi ring bioactivation. Those studied included heterocyclic amines (Glu-P- 1, Glu-P-2, IQ, MeIQ, Trp-P-1 and Trp-P-2), benzo[a]pyrene (B[a]P) and aflatoxin B1. However, CSC had no effect on the activity of direct-ac ting mutagens (2-nitrofluorene, sodium azide, 4-nitro-1,2-phenylenedia mine, 4-nitroquinoline N-oxide and methyl methanesulfonate). With indi rect-acting mutagens, the reduced number of revertants observed in the presence of CSC was not attributable to cytotoxicity. CSC exhibited a potent inhibitory effect on the cytochrome P-450 dependent monooxygen ases, ethoxyresorufin O-deethylase and B[a]P hydroxylase. This suggest s inhibition of the cytochrome P-450 isozymes as one possible mechanis m for the antimutagenicity of CSC. Fractionation studies of CSC reveal ed that the neutral, weakly acidic (phenolic) and basic fractions are all effective as antimutagens against Glu-P-1, a representative hetero cyclic amine. This indicates that several classes of chemicals contrib ute to the inhibitory effect of CSC on the mutagenicity of the heteroc yclic amines.