Serum increases CYP1A1 induction by 3-methylcholanthrene.
CYP1A1 is largely involved in carcinogenesis through the bioactivation of numerous procarcinogens. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) leads to induction of CYP1A1 via AhR pathway. We have previously demonstrated that fetal bovine serum (FBS) induces CYP1A1 gene transcription. In this work, we show evidence that the serum does not contain an AhR ligand and we evaluated the effect of a 3-methylcholanthrene (3-MC) and FBS cotreatment on CYP1A1 expression. CYP1A1 activity was potentiated by this treatment. This potentiation was at least in part associated with an increase of the CYP1A1 mRNA and gene transcription levels. FBS potentiation of CYP1A1 PAH-mediated induction was related to a significant increase of single strand breaks of DNA as compared to a single 3-MC treatment. Moreover, we demonstrated that human serum induces CYP1A1 with a high interindividual variability. The potentiation by serum of polycyclic aromatic hydrocarbon CYP1A1 induction could be involved in the etiology of some human cancers.
N'Guyen
Quoc-Binh
QB
UMR CNRS 6032, Faculté de Pharmacie, Université Méditerranée, 27 boulevard Jean Moulin, FR-13385, Marseille Cédex, France.
Fallone
Frederique
F
Seree
Eric
E
Fina
Frederic
F
Villard
Pierre-Henri
PH
Guigal
Nolwen
N
De Meo
Michel
M
Lacarelle
Bruno
B
Martin
Pierre-Marie
PM
Barra
Yves
Y
D000230:Adenocarcinoma; D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology; D001798:Blood Proteins / Q000494:pharmacology*; D002277:Carcinoma; D002417:Cattle; D003110:Colonic Neoplasms; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D004249:DNA Damage; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008748:Methylcholanthrene / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001551:Benz(a)Anthracenes; D001798:Blood Proteins; D012333:RNA, Messenger; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1