The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole

0365057 - ÚEM 2012 RIV US eng J - Journal Article
Mesárošová, M. - Valovičová, Z. - Srančíková, A. - Krajčovičová, Z. - Milcová, Alena - Sokolová, Romana - Schmuczerová, Jana - Topinka, Jan - Gábelová, A.
The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole.
Toxicology and Applied Pharmacology. Roč. 255, č. 3 (2011), s. 307-315. ISSN 0041-008X. E-ISSN 1096-0333
R&D Projects: GA MŠMT 2B08005
Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40400503; CEZ:AV0Z50040507
Keywords : cytochrome P4503A4 * 7H-dibenzo[c,g]carbazole * Hprt gene mutations
Subject RIV: DN - Health Impact of the Environment Quality
Impact factor: 4.447, year: 2011
http://arl-repository.lib.cas.cz/uloziste_av/UEM-P/cav_un_epca-0365057_01.pdf

The environmental pollutant 7H-dibenzo[c,g]carbazole (DBC) and its derivative, 5,9-dimethylDBC (DiMeDBC), produced significant and dose-dependent levels of micronuclei followed by a substantial increase in the frequency of apoptotic cells in the V79MZh3A4 cell line stably expressing the human cytochrome P450 (hCYP) 3A4. In contrast, neither micronuclei nor apoptosis were found in cells exposed to the sarcomagenic carcinogen, N-methylDBC (N-MeDBC). Based on our results, we suggest that hCYP3A4 is involved in the metabolism of DBC and its tissue-specific derivatives. While hCYP3A4 probably plays an important role in biotransformation of the liver carcinogens, DBC and DiMeDBC, it might only have a marginal function in N-MeDBC metabolism.
Permanent Link: http://hdl.handle.net/11104/0200393