Cigarette smoke condensates damage DNA in human lymphocytes

Abstract

THE carcinogenicity of tobacco tars and smoke in laboratory animals^1,2 together with epidemiological evidence from man have clearly suggested that smoking causes most lung cancer^3–5. 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 aberrations^13,14. Cytogenetic studies^15,16 have shown an increase in chromosomal aberrations in blood lymphocytes of heavy smokers relative to non-smokers, but little¹⁷ or no^16,18 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.