The effect of the genetic polymorphisms of CYP1A1,CYP2D6, GSTM1 and CSTP1 on aromatic DNA adduct levels in the population of healthy women

Aromatic DNA adduct levels and polymorphisms of two phase I enzymes - CYP1A 1 and CYP2D6 and two phase II enzymes - GSTM1 and GSTP1 were analyzed in a group of 133 nonsmoking healthy women 35-45 years old and holding jobs not connected with the exposure to the combustion products of organic matter. T hey were office workers from the south and north-eastern parts of Poland. B lood samples were collected in winter and in summer Aromatic DNA adduct lev els were measured in all winter and summer samples. The frequencies of CYP1 A1, CYP2D6, GSTM1 and GSTP1 polymorphisms in samples from the studied women did not show any differences when compared with other Caucasian population s and the Polish male population studied previously. The differences in the levels of DNA adducts among the carriers of different genotypes were stati stically non-significant. Analysis of combined genotypes selected the group s of volunteers with the highest and the lowest DNA adduct levels. The high est levels of DNA adducts were observed in the carriers of GSTM1 (null)/CYP 1A1Ile/Val (8.00+/-13.00 adducts/10(8) nucleotides in summer samples) and G STP1-AA/CYP1A1Ile/Val genotypes (7.00+/-4.32 in winter and 7.30+/-7.27/10(8 ) nucleotides in summer). The lowest levels of DNA adducts (3.00+/-2.30 in winter and 2.00+/-3.16/10(8) nucleotides in summer) were found in the carri ers of the genotype GSTP1-AG+GG/CYP1A1Ile/Val. The levels of DNA adducts in these groups were determined by the polymorphisms of GSTM1 and GSTP1 phase II detoxifying enzymes. (C) 2000 Published by Elsevier Science B.V.