PMID: 7581496Jan 1, 1995Paper

Metabolic polymorphism affecting DNA binding and excretion of carcinogens in humans

Pharmacogenetics
H BartschE Hietanen

Abstract

A case-control study on lung cancer patients demonstrated the pronounced effect of tobacco smoke on pulmonary carcinogen metabolism and suggested the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer. Lung cancer patients who were recent smokers showed in their lungs (i) significantly induced CYP1A1-related enzyme activity vs smoking non-lung cancer patients; (ii) increased benzo(a)pyrene (BP) tetrol formation from BP 7,8-diol by lung microsomes; and (iii) high levels of cytochrome P4501a1 by immunohistochemical staining. Levels of bulky aromatic DNA adducts (by 32P-postlabelling) and of BP-diol-epoxide (BPDE) adducts (by HPC/fluorometry) were quantified in lung parenchyma. Aryl hydrocarbon hydroxylase activity and the level of BPDE-DNA adducts (r = 0.91; p < 0.001) and to a lesser degree bulky DNA adducts were correlated. Thus pulmonary CYP1A1 expression (inducibility) controls in part polycyclic aromatic hydrocarbon-DNA adduct formation in tobacco smokers and, therefore, appears to be associated with lung cancer risk. High risk subjects for lung cancer among smokers may be identifiable through genotyping for polymorphic drug metabolizing enzymes in combination with molecular dosimetry of car...Continue Reading

Citations

May 12, 1997·Mutation Research·S MacLeodN P Lang
Jul 19, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Y W ChengH Lee
Jun 27, 2003·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Ya Wen Cheng, Huei Lee
May 1, 1996·Environmental Health Perspectives·H Bartsch, E Hietanen
Jun 1, 1997·Environmental Health Perspectives·E HietanenH Vainio
May 7, 1999·Environmental Health Perspectives·A Hirvonen
May 15, 2009·International Journal of Environmental Research and Public Health·Regina GrazulevicieneJone Vencloviene
Jan 1, 1996·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·M IchibaK Tomokuni
Dec 24, 2010·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·D Kalpana Deepa PriyaD Sakthisekaran
Jan 1, 1998·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·M IchibaK Tomokuni
Jan 1, 2000·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·M IchibaK Tomokuni
Feb 23, 2002·Journal of Exposure Analysis and Environmental Epidemiology·Terhi Kuljukka-RabbKimmo Peltonen

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