BACTERIAL MUTAGENICITY OF CIGARETTE-SMOKE AND ITS INTERACTION WITH ETHANOL

The mutagenicities of mainstream cigarette smoke (CS), a cigarette smo ke condensate (CSC) and smokers' urines were investigated by using bat teries of Salmonella typhimurium and Escherichia coil strains. The S9- mediated mutagenicity of CSC was remarkably enhanced when using nitror eductase- and especially O-acetyltransferase-overproducing derivatives of the classical strains TA98 and TA100, with the following rank of s ensitivity: YG1024 > YG1029 > YG1021 > TA98NR > YG1026 > TA98 > TA100 > TA100-DNP6 > TA100NR > TA98-1,8-DNP6. With YG1024, a doubling of spo ntaneous revertants was observed with as little as 1/110 of the smoke condensate recovered from one cigarette under our experimental conditi ons. Similarly, the SE-mediated mutagenicity of mainstream CS was cons iderably increased in YG1024 and YG1029, the O-acetyltransferase-overp roducing derivatives of TA98 and TA100, respectively. In the absence o f S9 mix, the concentrates of 23 urine specimens from five smokers fai led to revert S. typhimurium TA98 and YG1024, and were equitoxic in E. coli WP2 and its repair-deficient counterpart CM871 (uvrA(-), recA(-) , lexA(-)). In the presence of S9 mix, all specimens were mutagenic, w ith an average YG1024:TA98 ratio of 6.6:1. These patterns suggest that the bacterial mutagenicity of smoke-associated complex mixtures is ma inly due to aromatic amines. The mutagenicities of other typical const ituents of CS, i,e, the polycyclic aromatic hydrocarbon benzo[a]pyrene (BP) and the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK), were not appreciably enhanced in the O-acet yltransferase-overproducing strain YG1029, compared to its parental st rain TA100. Moreover, BP and NNK induced less than additive mutagenic responses when combined at high doses. It was possible to reproduce in vitro the synergism between CS and ethanol by exposing agar plates, i ncorporating bacteria (YG1024 or YG1029), S9 mix and ethanol, to mains tream CS. With YG1024, a considerable enhancement of CS mutagenicity w as observed with as low as 5 mu I volumes of ethanol. No synergism cou ld be conversely detected by using the classical tester strains TA98 a nd TA100.