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Biochem Biophys Res Commun ; 297(2): 249-54, 2002 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-12237110

RESUMEN

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.


Asunto(s)
Proteínas Sanguíneas/farmacología , Citocromo P-450 CYP1A1/biosíntesis , Metilcolantreno/metabolismo , Adenocarcinoma , Animales , Benzo(a)Antracenos/farmacología , Benzo(a)pireno/farmacología , Carcinoma , Bovinos , Neoplasias del Colon , Citocromo P-450 CYP1A1/genética , Daño del ADN , Inducción Enzimática/efectos de los fármacos , Humanos , ARN Mensajero/metabolismo , Células Tumorales Cultivadas
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