The effect of the genetic polymorphisms of CYP1A1,CYP2D6, GSTM1 and GSTP1 on aromatic DNA adduct levels in the population of healthy women.
Aromatic DNA adduct levels and polymorphisms of two phase I enzymes - CYP1A1 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. They were office workers from the south and north-eastern parts of Poland. Blood samples were collected in winter and in summer. Aromatic DNA adduct levels were measured in all winter and summer samples. The frequencies of CYP1A1, CYP2D6, GSTM1 and GSTP1 polymorphisms in samples from the studied women did not show any differences when compared with other Caucasian populations and the Polish male population studied previously. The differences in the levels of DNA adducts among the carriers of different genotypes were statistically non-significant. Analysis of combined genotypes selected the groups of volunteers with the highest and the lowest DNA adduct levels. The highest levels of DNA adducts were observed in the carriers of GSTM1(null)/CYP1A1Ile/Val (8.00+/-13.00 adducts/10(8) nucleotides in summer samples) and GSTP1-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 carriers 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.
Grzybowska
E
E
Department of Tumor Biology, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland. ewagrzybo@yahoo.com
Butkiewicz
D
D
Motykiewicz
G
G
Chorazy
M
M
D000328:Adult; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D018736:DNA Adducts / Q000097:blood*; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000378:metabolism; D011044:Poland; D011110:Polymorphism, Genetic; D012621:Seasons
D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D018736:DNA Adducts; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D009153:Mutagens; C496556:GSTP1 protein, human