Prevention of Human Mammary Carcinogenesis
Abstract
This study utilized the developed in vitro models and the identified biochemical and cellular markers to examine the induction of human mammary carcinogenesis by the environmental carcinogen Benzo(a)pyrene (BP), and its modulation by selected naturally-occurring tumor inhibitors. In the human mammary explant culture system BP treatment increased Ras p21-GTP binding, and replicative DNA synthesis, and altered the metabolism of 17B-estradiol (B2). Treatment of BP-initiated explant cultures with n-3 polyunsaturated fatty acid eicosapentaenoic acid or indole-3-carbinol inhibited replicative DNA synthesis and increased c2/Cl6a- hydroxylation of E2, thereby down-regulating BP-induced biomarker expression. In the human mammary epithelial cell culture system treatment with BP resulted in increased purine nucleotide adduct formation, arrest of the cell cycle in G2 + M phase and abrogation of cellular apoptosis. Treatment of BP-initiated cells with the soy isoflavone genistein inhibited the S phase and induced apoptosis. These results demonstrate that noninvolved human mammary tissue responds to the carcinogenic insult by perturbed expression of biochemical and cellular markers prior to tumorigenic transformation, and biomarker expression is down-regulated by the naturally-occurring tumor inhibitors. Thus, the biochemical and cellular markers represent quantitative endpoints for chemoprevention of human mammary carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 30, 1995
- Accession Number
- ADA298708
Entities
People
- Nitin T. Telang
Organizations
- Cornell University