Cigarette smoke condensates damage DNA in human lymphocytes

Abstract

THE carcinogenicity of tobacco tars and smoke in laboratory animals1,2 together with epidemiological evidence from man have clearly suggested that smoking causes most lung cancer3–5. However, other interpretations of the epidemiological evidence have been proposed6 and the carcinogens known to occur in cigarette smoke are present in only minute quantities7. There is increasing evidence that one prerequisite in the initiation of malignant transformation is an alteration in cellular DNA, and the findings that most carcinogens react with DNA8, that this reaction necessarily precedes transformation9 and that most carcinogens are mutagens10, support the importance of somatic mutation. Two types of visible chromosome changes that result from DNA damage are gross aberrations and symmetrical sister chromatid exchanges (SCE)11,12, and the induction of SCEs provides a very sensitive indicator of mutagen/carcinogen exposure at concentrations below those which normally result in the production of chromosomal aberrations13,14. Cytogenetic studies15,16 have shown an increase in chromosomal aberrations in blood lymphocytes of heavy smokers relative to non-smokers, but little17 or no16,18 increase in SCEs. Furthermore, products mutagenic to bacteria have been isolated from the urine of inhaling smokers19, and also smokers have a higher incidence of sperm abnormalities than non-smokers20. These studies imply that there may be higher levels of mutagens in body cells and fluids of smokers than in those of non-smokers, but little is known about the reaction of cigarette smoke with the DNA of exposed human cells, and even less about the possible mutagenic effects. Here we report that exposure of human lymphocytes to small quantities of tobacco smoke condensate leads to the formation of many DNA lesions that result in sister chromatid exchanges.