Excretion of mutagens, nicotine and its metabolites in urine of cigarette smokers.

Urine samples from 26 cigarette smokers on a restricted diet were collected in the late afternoon. Urine extracts on XAD-2 resin were tested for mutagenicity in the microsuspension assay using Salmonella typhimurium strain TA98 in the presence of metabolizing and deconjugating enzymes. Levels of urinary nicotine plus metabolites and cotinine were determined. Eighteen samples were clearly mutagenic, i.e. capable of doubling the number of spontaneous revertants at one of the assayed doses of urine. Urinary mutagenic activity ranged from 193 to 8462 net revertants/mmol of creatinine, while urinary nicotine plus metabolites and cotinine levels varied from 0.007 to 1.366 and from 0.011 to 0.297 mg/mmol creatinine. Urine samples with nicotine metabolite levels of < 0.33, 0.33- < 0.66 and > 0.66 mg/mmol creatinine had mean values +/- SD of mutagenic activity of 490 +/- 222 (n = 10), 964 +/- 560 (n = 9) and 2692 +/- 2807 (n = 7) revertants/mmol of creatinine, respectively, the statistical comparison between the groups being positive (Mann-Whitney U-test, P < 0.05). The mutagenic activity of urine samples from smokers correlated well with urinary nicotine plus metabolite levels (r = 0.658, P < 0.01). A less close correlation was found between urinary mutagenic activity and other indicators of tobacco smoke exposure, such as urinary cotinine (r = 0.504, P < 0.05), number of cigarettes smoked during the day of urine collection (r = 0.399, P < 0.05) and machine smoking-derived nicotine deliveries of the total number of cigarettes smoked (number of cigarettes multiplied by the nicotine content of each cigarette, as indicated by the manufacturer; r = 0.439, P < 0.05). These results suggest that the mutagenic activity of smokers' urine may be predicted by the urinary level of nicotine plus metabolites. The low degree of reliability of many presumptive indicators of exposure to tobacco smoke and the different urinary excretion kinetics of tobacco smoke mutagens with respect to cotinine (a frequently used biomarker for monitoring exposure to tobacco smoke) are both emphasized.