LYMPHOCYTES, DNA-ADDUCTS AND GENETIC-POLYMORPHISM FOR METABOLIC ENZYMES IN LOW-DOSE CIGARETTE SMOKERS

The aim of this study was to investigate the relationship between gene tic polymorphism of metabolic enzymes and DNA adduct levels in lymphoc ytes of low dose cigarette smokers (less than 20 cigarettes per day). We previously reported the effects of cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) on lymphocyte DNA adducts. This t ime we considered not only CYP1A1 and GSTM1 but also cytochrome P4502E 1 (CYP2E1) and glutathione S-transferase T1 (GSTT1). DNA adducts in ly mphocytes obtained from low dose cigarette smokers (n=41) and nonsmoke rs (n=56) were measured by the P-32-postlabelling method. The adduct l evels were compared regarding smoking status and polymorphic genotypes of these four enzymes. The mean +/- SD of DNA adduct levels in all lo w dose cigarette smokers and non-smokers was 1.05 +/- 0.83 per 10(8) n ucleotides and 0.85 +/- 0.33 per 10(8) nucleotides, respectively. In l ow dose cigarette smokers, adduct levels were higher in the rare homoz ygous (MM) for CYP1A1-exon 7 polymorphism compared with the other type s such as common homozygous (WW) and heterozygous (WM). CYP1A1-WM, MM in combination with GSTM1 null showed highest adduct level among low s mokers. The low smokers with rare homozygous for CYP2E1 Dra1 polymorph ism tended to have lower adduct levels than wild types. Low dose cigar ette smokers with combined GSTM1 null and T1 null had a higher tendenc y for adduct levels than others. However none of the differences reach ed statistical significance.