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Molecular mechanisms of estrogen carcinogenesis.
The examples demonstrate that the parent compounds and their metabolites cause both nongenotoxic cell proliferative effects as well as direct and indirect genotoxic effects, which illustrates the complex nature of estrogen carcinogenesis. Expand
Is estradiol a genotoxic mutagenic carcinogen?
- J. Liehr
- Medicine, Biology
- Endocrine reviews
- 1 February 2000
Data suggest that E2 is a weak carcinogen and weak mutagen capable of inducing genetic lesions with low frequency and may develop by hormone receptor-mediated proliferation of such damaged cells. Expand
Free radical generation by redox cycling of estrogens.
The in vivo activities of enzymes supporting redox cycling of estrogens and free radical generation is correlated with induction of kidney tumors in Syrian hamsters, suggesting a role of free radicals in the induction of tumors by estrogen. Expand
Carcinogenicity of catechol estrogens in Syrian hamsters.
4-hydroxyestradiol was found to be as carcinogenic as estradiol in male Syrian hamsters and consistent with a role of catechol metabolites in estrogen-induced carcinogenesis, however, the intrinsic carcinogenic or hormonal activity of 2-hydrogens probably can not be assessed accurately in vivo because of its rapid methylation and metabolic clearance. Expand
Tissue-specific synthesis and oxidative metabolism of estrogens.
- C. Jefcoate, J. Liehr, +10 authors L. Berstein
- Journal of the National Cancer Institute…
- 1 July 2000
Evidence in support of the role of P4501B1 as the 4-hydroxylase expressed in human breast tissue is reviewed and the hypothesis that sufficient E2 may be present in tissue for formation of catechol metabolites that are estrogenic and which form genotoxic species at levels that may contribute to estrogen carcinogenesis is questioned. Expand
Role of iron in estrogen-induced cancer.
A role of iron in hormone-associated cancer in humans offers attractive routes for cancer prevention by regulating metal ion metabolism and interfering with iron accumulation in tissues. Expand
Induction of covalent DNA adducts in rodents by tamoxifen.
The accumulation of DNA adducts with repeated administrations of tamoxifen to rodents may make this drug a poor choice for the chronic preventative treatment of breast cancer. Expand
8-Hydroxylation of guanine bases in kidney and liver DNA of hamsters treated with estradiol: role of free radicals in estrogen-induced carcinogenesis.
Levels of 8-hydroxy-2'-deoxyguanosine, a marker product of hydroxy radical interaction with DNA, in livers and kidneys of hamsters treated with estradiol support a mechanism of estrogen-induced carcinogenesis by free radicals generated via redox cycling of catecholestrogen metabolites. Expand
Dual role of oestrogens as hormones and pro-carcinogens: tumour initiation by metabolic activation of oestrogens.
- J. Liehr
- Biology, Medicine
- European journal of cancer prevention : the…
- 1 February 1997
A mechanism for mammary carcinogenesis is examined, which emphasizes tumour initiation by metabolic activation of oestrogens in combination with cell transformation and growth stimulation by oestrogen receptor-mediated processes. Expand