Study on metabolism of 3-aminobenzanthrone and induction of biotransformation enzymes

CHARLES UNIVERSITY IN PRAGUE FACULTY OF SCIENCE DEPARTMENT OF BIOCHEMISTRY Study on metabolism of 3-aminobenzanthrone and induction of biotransformation enzymes Summary of PhD Thesis RNDr. Jana Mizerovská Supervisor: Prof. RNDr. Marie Stiborová, DrSc. Prague 2010 RNDr. Jana Mizerovská Introduction 1 INTRODUCTION 3-Nitrobenzanthron, precursor of 3-ABA The nitroaromatic 3-nitrobenzanthrone (3-nitro-7H-benz de anthracen-7-one, 3-NBA) occurs in diesel exhaust and in airborne particulate matter(8, 9, 14) . 3-NBA is most likely formed during the atmospheric reaction of benzanthrone with nitrogen oxides, especially in the presence of ozone, or during imperfect burning of diesel. 3-NBA exhibits extremely high mutagenic activity(9, 14) and is also a genotoxic carcinogen causing lung tumors in rats(14) . 3-NBA is also evaluated to be a potential carcinogen for humans(14, 1, 9, 19) . The genotoxicity of 3-NBA was documented by the detection of specific 3-NBA-derived DNA adducts in vitro, in human cell lines and also in vivo in rats and mice(12, 13, 15, 2) . The predominant DNA adducts formed by 3-NBA after its metabolic activation by reduction of the nitro group are 2-(2'-deoxyguanosin-N2 -yl)-3- aminobenzanthrone and N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone(9, 14) and these are most probably responsible for the..