Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model.

Abstract:

:We have previously shown that chronic activation of mitogenic signaling induced by over-expression of c-myc and transforming growth factor-alpha (TGFalpha) transgenes in mouse liver induces a state of oxidative stress. We therefore proposed that increased reactive oxygen species (ROS) generation might be responsible for the extensive chromosomal damage and acceleration of hepatocarcinogenesis characteristic for TGFalpha/c-myc mice. In this study, we show that vitamin E (VE), a potent free radical scavenging antioxidant, is able to protect liver tissue against oxidative stress and suppress tumorigenic potential of c-myc oncogene. Dietary supplementation with VE, starting from weaning, decreased ROS generation coincident with a marked inhibition of hepatocyte proliferation while increasing the chromosomal as well as mtDNA stability in the liver. Similarly, dietary VE reduced liver dysplasia and increased viability of hepatocytes. At 6 mo of age, VE treatment decreased the incidence of adenomas by 65% and prevented malignant conversion. These results indicate that ROS generated by over-expression of c-myc and TGFalpha in the liver are the primary carcinogenic agents in this animal model. Furthermore, the data demonstrate that dietary supplementation of VE can effectively inhibit liver cancer development.

authors

Factor VM,Laskowska D,Jensen MR,Woitach JT,Popescu NC,Thorgeirsson SS

doi

10.1073/pnas.040428797

keywords:

subject

Has Abstract

pub_date

2000-02-29 00:00:00

pages

2196-201

issue

5

eissn

0027-8424

issn

1091-6490

pii

040428797

journal_volume

97

pub_type

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