Bacterial mutagenicity of cigarette smoke and its interaction with ethanol.
The mutagenicities of mainstream cigarette smoke (CS), a cigarette smoke condensate (CSC) and smokers' urines were investigated by using batteries of Salmonella typhimurium and Escherichia coli strains. The S9-mediated mutagenicity of CSC was remarkably enhanced when using nitroreductase- and especially O-acetyltransferase-overproducing derivatives of the classical strains TA98 and TA100, with the following rank of sensitivity: YG1024 > YG1029 > YG1021 > TA98NR > YG1026 > TA98 > TA100 > TA100-DNP6 > TA100NR > TA98-1,8-DNP6. With YG1024, a doubling of spontaneous revertants was observed with as little as 1/110 of the smoke condensate recovered from one cigarette under our experimental conditions. Similarly, the S9-mediated mutagenicity of mainstream CS was considerably increased in YG1024 and YG1029, the O-acetyltransferase-overproducing derivatives of TA98 and TA100, respectively. In the absence of S9 mix, the concentrates of 23 urine specimens from five smokers failed 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, with an average YG1024:TA98 ratio of 6.6:1. These patterns suggest that the bacterial mutagenicity of smoke-associated complex mixtures is mainly due to aromatic amines. The mutagenicities of other typical constituents 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-acetyltransferase-overproducing strain YG1029, compared to its parental strain TA100. Moreover, BP and NNK induced less than additive mutagenic responses when combined at high doses.(ABSTRACT TRUNCATED AT 250 WORDS)
De Flora
S
S
Institute of Hygiene and Preventive Medicine, University of Genoa, Italy.
Balansky
R
R
Gasparini
L
L
Camoirano
A
A
D000123:Acetyltransferases / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001711:Biotransformation; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D009153:Mutagens / Q000302:isolation & purification / Q000633:toxicity; D009601:Nitroreductases / Q000378:metabolism; D010947:Plants, Toxic; D011355:Prodrugs / Q000302:isolation & purification / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis; D012907:Smoking / Q000652:urine*; D013045:Species Specificity; D014026:Nicotiana
D001426:Bacterial Proteins; D009153:Mutagens; D011355:Prodrugs; D012906:Smoke; D000431:Ethanol; D009601:Nitroreductases; D000123:Acetyltransferases