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Metabolism of Cigarette Smoke Condensates by Human and Rat Homogenates to Form Mutagens Detectable by Salmonella typhimurium TA1538¹

Department of Medicine, Veterans Administration Hospital, Lexington 40507 [J. J. H., C. H.], and University of Kentucky School of Medicine, Lexington, Kentucky 40506 [J. J. H.]

Nineteen fractions of whole condensate of smoke from the University of Kentucky Reference Cigarette IRI were tested for mutagenicity in vitro using a bacterial indicator system. As little as 25 µg of the active fractions were mutagenic toward histidine-requiring Salmonella typhimurium TA1538, if the condensates were incubated in the presence of rat or human liver homogenates during treatment of the bacteria. Homogenates of lung were relatively inactive. Homogenates from livers of rats that had been treated with 3-methylcholanthrene converted condensates to mutagens more efficiently than did liver homogenates from man or from normal or phenobarbital-treated rats. Use of homogenates from animals treated with 3-methylcholanthrene gave much more reproducible results in smoke fraction assays because larger numbers of revertants were obtained, and dose-response curves were linear over the range 25 to 250 µg condensate. The linear dose-response curves permitted quantitative comparison of the various fractions. The mutagenicity per mg of basic fractions of whole smoke condensate is very high and that of neutral polycyclic hydrocarbons is very low. Because of the exquisite preferential sensitivity of the TA1538 test system to polycyclic amines and insensitivity to alkyl polycyclics, there is a poor quantitative correlation between mutagenicity and carcinogenicity, as measured by skin painting or in vitro cell transformation. There is substantial evidence that many carcinogens are mutagens but that most of these compounds require metabolism before they are biologically active. If further development improves the sensitivity of the bacterial testing system to mutagenic derivatives of alkyl polycyclic and heteropolycyclic hydrocarbons, it may provide a convenient, rapid, quantitative, and inexpensive bioassay for the detection of potentially carcinogenic substances in tobacco smoke condensates.

¹ This study was carried out under Contract 12-14-7001-293 with the Agricultural Research Service, U. S. Department of Agriculture, administered by the Athens, Georgia Area, Richard B. Russell Agricultural Research Center, Athens, Ga. 30604. It was also supported in part by Veterans Administration Project No. MRIS 3843-04, University of Kentucky Tobacco and Health Research Institute Project No. KTRB 043, and Grant AM 16013 from the NIH.

Received 12/16/74. Accepted 5/29/75.