Effects of alpha-naphthoflavone on levels of sister chromatid exchanges in lymphocytes from active and passive cigarette smokers: dose-response relationships.

The frequency of sister chromatid exchanges (SCE) were determined in lymphocytes of nonsmokers, passive smokers, and active smokers in the presence and absence of alpha-naphthoflavone (ANF). Higher levels of SCEs were detected for all smoking groups after in vitro addition of ANF when compared with an assay without ANF. There was a highly statistically significant difference between heavy smokers and nonsmokers (9.25 versus 7.43 SCE/cell) for the assay without ANF and for the ANF assay (14.2 versus 8.8). When considering the numerical difference in SCEs between the assays with and without ANF (delta SCE), higher values were noted for moderate smokers (2.7) and heavy smokers (4.9) compared to nonsmokers (1.4). Significant dose-response relationships were found between the frequency of SCEs and factors related to smoking, such as duration and frequency of cigarette use, tar, nicotine, carbon monoxide content of brand, and urinary measures of nicotine metabolites (cotinine and thiocyanate). No elevation of SCEs in passive smokers was found when compared to nonsmokers using either assay. The mechanism for SCE enhancement by ANF is unclear, but may be related to metabolic activation of the ANF by the cytochrome P-450 system in lymphocytes. The dosimetry relationships between cigarette smoke exposure and SCE frequency indicate that culture of human lymphocytes via ANF may provide a sensitive tool to detect exposure to cigarette smoke.