Ferritin H, CYP1A1, and CYP1B1 Altered Expression in Mexican Tobacco Smokers

Abstract

ISEE-635 Objective: Tobacco smoke is a chemical mixture where many constituents are human carcinogens and regulate the genes expression. The aim of this study was to detect the CYP 1A1, 1B1, and Ferritin mRNA levels and CYP 1A1, 1B1, and GSTM polymorphisms, as possible biomarkers of exposure and susceptibility, respectively in smokers. Materials and Methods: A cross-sectional study was carried out in 102 male unrelated smokers aged 18 to 53 years. Participants were directly interviewed by trained personnel and clinical, occupational, and sociodemographic characteristics. Tobacco exposure was estimated by interview, urinary cotinine, and 1-OHP levels. CYP 1A1, 1B1, and Ferritin H mRNA were evaluated in peripheral lymphocytes by quantitative real-time PCR. GSTM polymorphism was analyzed using a duplex PCR assay and CYP1A1 (Ile462Val) and CYP1B1 (1Leu432Val) polymorphisms were determined by real-time PCR-TaqMan System. All subjects gave written consent after being fully informed about the purpose and nature of the study that was approved by the Ethical Committee of CINVESTAV-IPN. Results: The frequencies of CYP1A1 alleles in our population were 35.2 native, 50.5 heterozygote, and 14.3% mutant, and the frequencies of CYP1B1 were 52.7 native, 37.6% heterozygote, and 9.7% mutated. The polymorphism GSTM1 showed 38% of population were type GSTM1 null allele (GSTM1−/−). In addition the cotinine urinary medium was 4101.43 ng/mL (1210–5789) and the mean value of 1-OHP was 5279.5 nmol/L (0–91756.6). A high correlation between the concentrations of 1-OHP and cotinine was found. A wide variation in gene expression among the samples was observed; however, CYP1B1 gene was related with the cotinine levels (β = 71.31, P = 0.011), and the CYP1B1 polymorphism did not modified this relationship. Conclusions: Our preliminary results suggest specific changes in gene expression of genes in lymphocytes of smokers; and its implications for the metabolic activation of procarcinogens to ultimate carcinogens of tobacco smoke were studied.