Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes.
Aromatic amines have been shown to cause bladder cancer. However, epithelial cells of the urinary bladder, cells of origin of bladder cancer, may be exposed to numerous substances besides aromatic amines. In the present study, we analysed possible interactions between the aromatic amines 4-aminobiphenyl (4-ABP) as well as 2-naphthylamine (2-NA) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). For this purpose we incubated primary porcine urinary bladder epithelial cells (PUBEC) with concentrations of 1 to 50 microM 4-ABP with and without co-exposure to B[a]P. As expected B[a]P increased mRNA expression of cytochrome P450 1A1 (CYP1A1), whereas 4-ABP had no effect. However, when co-exposed 4-ABP enhanced the induction of CYP1A1 by B[a]P. This result was confirmed by Western blot analysis of CYP1A1 protein expression. A similar effect as for CYP1A1 was also observed for cyclooxygenase-2 (COX-2) and UDP-glucuronosyltransferase 1 (UGT1). Next, we studied co-exposures of 2-NA and B[a]P. Similar as for 4-ABP also 2-NA enhanced B[a]P-mediated induction of CYP1A1. Our results demonstrate that some aromatic amines may enhance the influence of B[a]P on Ah receptor-dependent genes.
Borza
Alexandra
A
Max-Planck Institut für molekulare Physiologie, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.
Plöttner
Sabine
S
Wolf
Alexander
A
Behm
Claudia
C
Selinski
Silvia
S
Hengstler
Jan G
JG
Roos
Peter H
PH
Bolt
Hermann M
HM
Kuhlmann
Jürgen
J
Föllmann
Wolfram
W
D015081:2-Naphthylamine / Q000378:metabolism*; D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D034421:Sus scrofa; D001743:Urinary Bladder / Q000166:cytology
D000611:Aminobiphenyl Compounds; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C006757:4-biphenylamine; D001564:Benzo(a)pyrene; D015081:2-Naphthylamine