Inhibition of cell death in human mammary epithelial cells by the cooked meat-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen present in the human diet in cooked meat. To examine if PhIP and its reactive metabolite N-hydroxy-PhIP inhibit apoptosis in human mammary epithelial MCF-10A cells, confluent cultures deprived of serum and growth factors were incubated for 24 h with either compound. The percentages of dead cells (mean +/- SEM, n = 3) as measured by trypan blue exclusion were 5.7 +/- 0.6, 3.4 +/- 0.3, 2.7 +/- 0.3, and 0.2 +/- 0.003%, in control, 1 microM N-hydroxy-PhIP-, 5 microM N-hydroxy-PhIP-, and 100 microM PhIP-treated dishes, respectively. The expression of Bcl-2 and Bcl-x(L) as quantitated by Western blotting was 1.2- to 1.9-fold higher in the treated groups. PhIP-DNA adducts induced by N-hydroxy-PhIP in MCF-10A cells measured by the (32)P-postlabeling assay were low (<1 x 10(7), relative adduct labeling). No adducts were detected after incubation with PhIP. Western blot analysis indicated that PhIP increased ERK2 phosphorylation concomitant with Bcl-2. The results suggest that the inhibition of cell death in mammary epithelial cells by PhIP occurs independently of PhIP-DNA adducts and may involve enhanced signaling through the MAP kinase pathways.

Venugopal M ，Agarwal R ，Callaway A ，Schut HA ，Snyderwine EG ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

Detection of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer.

Zhu J ，Chang P ，Bondy ML ，Sahin AA ，Singletary SE ，Takahashi S ，Shirai T ，Li D ... -  《CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION》

The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine activates the extracellular signal regulated kinase mitogen-activated protein kinase pathway.

Creton SK ，Zhu H ，Gooderham NJ 《-》

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) modulates lactogenic hormone-mediated differentiation and gene expression in HC11 mouse mammary epithelial cells.

Shan L ，Rouhani SA ，Schut HA ，Snyderwine EG ... -  《-》

Cytotoxicity, DNA adduct formation and DNA repair induced by 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine in cultured human mammary epithelial cells.

Fan L ，Schut HA ，Snyderwine EG 《CARCINOGENESIS》