Arsenite inhibition of CYP1A1 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin is independent of cell cycle arrest.

We show here that arsenite (As(3+)) elicits multiple effects on gene control, such as the interruption of cell cycle control by initiating G(2)/M arrest as well as inhibiting the aryl hydrocarbon (Ah) receptor-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible expression of CYP1A1. This raises the question as to whether As(3+) is selectively inhibiting TCDD induction of CYP1A1 independent of cell cycle control. As(3+) stimulated a concentration-dependent increase in G(2)/M phase arrest that was detected at 12.

The human CYP1A1 gene is regulated in a developmental and tissue-specific fashion in transgenic mice.

Regulation and expression of human CYP1A1 is demonstrated in transgenic mice. We have developed two transgenic mouse lines. One mouse strain (CYPLucR) carries a functional human CYP1A1 promoter (-1612 to +293)-luciferase reporter gene, and the other strain (CYP1A1N) expresses CYP1A1 under control of the full-length human CYP1A1 gene and 9 kb of flanking regulatory DNA.

Identification and functional characterization of UDP-glucuronosyltransferases UGT1A8*1, UGT1A8*2 and UGT1A8*3.

UDP-glucuronosyltransferase (UGT) 1A8 is part of the UGT1 locus and is expressed exclusively in extrahepatic tissues. Analysis of UGT1A8 exon 1 sequence has identified four genotypes from a population of 69 individuals. While there are four alleles, one of the single base pair changes leads to a silent mutation at T255, while the other mutations lead to amino acid substitutions at positions 173 and 277, creating three allelic variants.

Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in Caco-2 cells--potential role in carcinogen bioinactivation.

Purpose: Dietary flavonoids, present in fruits, vegetables and beverages have been demonstrated to be protective in cancer. Recently, we showed that the flavonoid chrysin induced UDP-glucuronosyltransferase (UGT) activity and expression in the human intestinal cell line Caco-2. In the present study, we determined the specific UGT isoform(s) induced and whether this induction facilitates glucuronidation and potential detoxification of the colon carcinogen 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP).

Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in the human hepatoma cell line hep G2.

The UDP-glucuronosyltransferases (UGTs) have long been known to be inducible by various chemicals, including drugs, although the extent of induction in general has been modest. In the present study, we determined the ability of the dietary flavonoid chrysin to induce UGT activity, protein and mRNA. When pretreating human hepatoma Hep G2 cells with 25 microM chrysin, the glucuronidation of chrysin itself increased 4.