Methylation profile and amplification of proto-oncogenes in rat pancreas induced with phytoestrogens
- National Center for Toxicological Research, Jefferson, AR (United States)
Specific gene hypermethylation has been shown in DNA from neonatal rats exposed to the phytoestrogens, coumestrol, and equol. The pancreas is an organ in which estrogen receptors have been shown to be present. Studies have correlated the development of acute pancreatitis with rising levels of human estrogen binding proteins. Neonatal rats were dosed with 10 or 100 {mu}g of coumestrol or equol on postnatal day (PND) 1-10. The animals were sacrificed at Day 15. The pancreas was excised and pancreatic acinar cells isolated for molecular analysis. DNA was isolated from the cells by lysis in TEN-9 buffer supplemented with proteinase K and 0.1% SDS. High molecular weight (HMW) DNA was digested with the methylated DNA specific restriction enzymes, Hpa II and Msp I, for determination of methylation profiles. Both coumestrol and equol at high doses caused hypermethylation of the c-H-ras proto-oncogene. No hypermethylation or hypomethylation was observed in the proto-oncogenes, c-myc or c-fos. Methylation is thought to be an epigenetic mechanism involved in the activation (hypomethylation) or inactivation (hypermethylation) of cellular genes which are known to play a role in carcinogenesis. Epidemiology studies have shown that equol may have anti-carcinogenic effects on some hormone-dependent cancers. Additional studies are needed to further understand the role of phytoestrogens and methylation in relation to pancreatic disorders. 15 refs., 4 figs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 241022
- Journal Information:
- Proceedings of the Society for Experimental Biology and Medicine, Vol. 208, Issue 1; Other Information: PBD: Jan 1995
- Country of Publication:
- United States
- Language:
- English
Similar Records
Elevated expression of proto-oncogenes accompany enhanced induction of heat-shock genes after exposure of rat embryos in utero to ionizing irradiation
Control of c-fos and c-myc proto-oncogene induction in rat thyroid cells in culture