Is estradiol a genotoxic mutagenic carcinogen?

Endocrine Reviews

Volumn 21, Issue 1, 2000, Pages 40-54

  Liehr, Joachim G ^a  

^a Stehlin Found for Cancer Research   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 HYDROXYESTRADIOL; CYTOCHROME P450 1B1; ESTRADIOL; GESTAGEN;

ANEUPLOIDY; BREAST CANCER; CANCER RISK; CARCINOGENESIS; CARCINOGENICITY; CELL CULTURE; CELL DAMAGE; CELL FREE SYSTEM; CELL PROLIFERATION; CHROMOSOME ABERRATION; CHROMOSOME DAMAGE; CLINICAL TRIAL; DNA DAMAGE; DNA MODIFICATION; DOSE RESPONSE; GENE AMPLIFICATION; GENE MUTATION; GENETIC DAMAGE; GENOTOXICITY; HORMONE ACTION; HORMONE METABOLISM; HORMONE STRUCTURE; HUMAN; META ANALYSIS; MICROSATELLITE INSTABILITY; MUTAGENICITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; UTERUS CANCER;

ANIMALS; ARYL HYDROCARBON HYDROXYLASES; CARCINOGENS; CHROMOSOMES; ESTRADIOL; HUMANS; MUTAGENS;

EID: 0034463957     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.21.1.40     Document Type: Review

References (203)

1. Demonstration of a direct carcinogenic effect of estradiol on Leydig cells of the mouse
2. Osseous changes and osteosarcomas in mice continuously fed diets containing diethylstilbestrol or 17β-estradiol
3. 3H mice by diets containing diethylstilbestrol or 17β-estradiol
4. Long-term effects of progesterone or diethylstilbestrol with or without estrogen after maturity on mammary tumorigenesis in mice
5. Protective effects of progesterone and tamoxifen in estrogen-induced mammary carcinogenesis in ovariectomized W/Fu rats
6. Spontaneous and estrogen-produced tumors in Nb rats and their behaviour after transplantation
7. Ovary intact, but not ovariectomized female ACI rats treated with 17β-estradiol rapidly develop mammary carcinoma
8. Estrogen-induced tumors of the kidney. III. Growth characteristics in the Syrian hamster
9. Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney
10. Estrogen-induced tumorigenesis in hamsters: Roles for hormonal and carcinogenic activities
11. Hormonal carcinogenesis: Separation of estrogenicity from carcinogenicity
12. Structure and origin of uterine and extragenital fibroids induced experimentally in the guinea pig by prolonged administration of estrogens
13. 3H/HeJ female mice: Counteraction by concurrent 2-bromo-α-ergocryptine
14. 3H mice continuously fed diets containing diethylstilbestrol or 17β-estradiol
15. Rodent carcinogens: Setting priorities
16. DNA lesions, inducible DNA repair, and cell division: Three key factors in mutagenesis and carcinogenesis
17. Endometrial cancer after menopausal use of estrogens
18. Hormonal basis of risk factors for breast and endometrial cancer
19. The dose-effect relationship between "unopposed" estrogens and endometrial mitotic rate: Its central role in explaining and predicting endometrial cancer risk
20. Risk factors for endometrial cancer
21. Estrogens and breast cancer
22. The epidemiology of breast cancer
23. A prospective study of endogenous estrogens and breast cancer in post-menopausal women
24. Estrogen metabolism and excretion in oriental and caucasian women
25. Hormonal chemoprevention of cancer in women
26. Sex hormone levels in serum in relation to the development of breast cancer
27. Sex hormones and postmenopausal breast cancer: A prospective study in an adult community
28. Serum sex hormone levels after menopause and subsequent breast cancer
29. Serum oestrogen levels in postmenopausal women: Comparison of American whites and Japanese in Japan
30. Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles; Results from two breast cancer case-control studies
31. Hormone levels in older women: A study of post-menopausal breast cancer patients and healthy population controls
32. The role of estrogens and progestogens in the epidemiology and prevention of breast cancer
33. Toward the primary prevention of cancer
34. Steroid hormones and risk of breast cancer
35. The use of estrogens and progestins and the risk of breast cancer in post-menopausal women
36. Progestin regulation of cellular proliferation
37. Exogenous hormones and breast cancer risk
38. Breast cancer and hormone replacement therapy: Collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer
39. The steroid and thyroid hormone receptor superfamily
40. The nuclear receptor superfamily: The second decade
41. Molecular mechanisms of action of steroid/thyroid receptor superfamily members
42. Mechanisms of estrogenic and antiestrogenic regulation of growth of human breast carcinoma
43. Rapid, nongenomic actions of estrogens
44. Regulation of cell proliferation: Is the ultimate control positive or negative?
45. Estrogen receptors: Bioactivity and interactions with cell signaling pathways
46. Inhibition of estrogen-induced renal carcinogenesis in male Syrian hamsters by Tamoxifen without decrease in DNA adduct levels
47. Role of hormones in mammary neoplasia
48. Estrogen carcinogenesis in hamster tissues: Update
49. Non-mutagenicity of some sex hormones in the Salmonella/microsome mutagenicity test
50. Carcinogenicity of catechol estrogens in Syrian hamsters
51. Studies for a genotoxic potential of some endogenous and exogenous sex steroids. I. Communication: Examination for the induction of gene mutations using the Ames Salmonella/microsome test and the HGPRT test in V79 cells
52. Mutagenicity assays of estrogenic hormones in mammalian cells
53. The mutagenic potential of antiestrogens at the HPRT locus in V79 cells
54. Sister chromatid exchanges and cell division delays induced by diethylstilbestrol, estradiol, and estriol in human lymphocytes
55. Hormones as etiological agents in neoplasia
56. Dissociation between steroid receptor expression and cell proliferation in human breast
57. Pattern of distribution of cells positive for estrogen receptor α and progesterone receptor in relation to proliferating cells in the mammary gland
58. 2-Fluoroestradiol: Separation of estrogenicity from carcinogenicity
59. Estradiol 16α-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: A possible model for the hormonal etiology of breast cancer in humans
60. Abnormal oxidative metabolism of estradiol in women with breast cancer
61. Covalent binding of the endogenous estrogen 16α-hydroxyestrone to estradiol receptor in human breast cancer cells: Characterization and intranuclear localization
62. Omega-3 fatty acids: Modulations of estrogen metabolism and potential for breast cancer prevention
63. Metabolic biotransformation of estradiol in human mammary explant cultures
64. Molecular and endocrine biomarkers in non-involved breast: Relevance to cancer chemoprevention
65. 3H mouse
66. Preneoplastic transformation in mouse mammary tissue: Identification and validation of Intermediate biomarkers for chemoprevention
67. Persistent estrogen responsiveness of ras oncogene-transformed mouse mammary epithelial cells
68. Biotransformation of estradiol by explant culture of human mammary tissue
69. Radiometric analysis of biological oxidations in man: Sex differences in estradiol metabolism
70. Radioimmunoassay of 16α-hydroxyestrone in human urine
71. 3H]estradiol by rabbit hypothalami in vitro
72. Catechol estrogen formation and metabolism in brain tissue: Comparison of tritium release from different positions in ring A of the steroid
73. Biogenesis of catecholestrogens: Metabolic activation of estrogens by phase I enzymes
74. Metabolism of estrogens by target cells. Diversification and amplification of hormone action and the catecholestrogen hypothesis
75. 16-Hydroxylation of steroidal estrogens by rodent and human microsomes
76. Upregulation of estradioi C16α-hydroxylation in human breast tissue: A potential biomarker of breast cancer risk
77. Urinary 2-hydroxyestrone/16 α-hydroxyestrone ratio and risk of breast cancer in postmenopausal women
78. 1) in postmenopausal women with and without breast cancer
79. 17β-Estradiol-induced cell transformation and aneuploidy of Syrian hamster embryo cells in culture
80. Diethylstilbestrol induces neoplastic transformation without measurable gene mutation at two loci
81. Mechanisms of estrogen-associated carcinogenesis
82. Aneuploidy induction and cell transformation by diethylstilbestrol: A possible chromosomal mechanism in carcinogenesis
83. Neoplastic transformation of cultured mammalian cells by estrogens and estrogen-like chemicals
84. Nonrandom karyotypic changes in a spontaneously immortalized and tumorigenic Syrian hamster embryo cell line
85. Genetic instabilities in human cancers
86. Hormones and carcinogenesis: Laboratory studies
87. Estrogen carcinogenesis in the hamster kidney: A hormone-driven multi-step process
88. Perspectives in hormonal carcinogenesis. Animal models to human disease
89. Estrogen-induced proto-oncogene and suppressor gene expression in the hamster kidney: Significance for estrogen carcinogenesis
90. Sex hormones and neoplastic transformation
91. Estrogen carcinogenesis in the hamster kidney: Role of cytotoxicity and cell proliferation
92. Estrogen carcinogenesis in hamster tissues: A critical review
93. Overexpression and amplification of c-myc in the Syrian hamster kidney during estrogen carcinogenesis: A probable critical role in neoplastic transformation
94. Estrogen 2-/4-hydroxylase activity, catechol estrogen formation and implications for estrogen carcinogenesis
95. Regulation of estrogen 2-/4-hydroxylase activity in hamster kidney by estrogens and androgens
96. Catechol formation of fluoro- and bromo-substituted estradiol by hamster liver microsomes: Evidence for dehalogenation
97. DNA adduct profiles in hamster kidney following chronic exposure to various carcinogenic and non-carcinogenic estrogens
98. 32P-postlabelling in studies of hormonal carcinogenesis
99. Microsomal hydroxylation of 2- and 4-fluoroestradiol to catechol metabolites and their conversion to methyl ethers: Catechol estrogens as possible mediators of hormonal carcinogenesis
100. Metabolism of moxestrol in the hamster kidney: Significance for estrogen carcinogenesis
101. Catechol estrogen-forming enzyme of brain: Demonstration of a cytochrome P450 monooxygenase
102. Relative rates of 2- and 4-hydroxyestrogen synthesis are dependent on both substrate and tissue
103. Comparison of assays for catechol estrogen synthase activity: Product isolation vs. radioenzymatic catechol-O-methyltransferase-coupled procedures
104. The O-methylation of 4-hydroxyestradiol is inhibited by 2-hydroxyestradiol: Implications for estrogen-induced carcinogenesis
105. Monooxygenase mediating catecholestrogen formation by rat anterior pituitary is an estrogen-4-hydroxylase
106. Catechol estrogen formation in the mouse uterus and its role in implantation
107. Elevated 4-hydroxylation of estradiol by hamster kidney microsomes: A potential pathway of metabolic activation of estrogens
108. The carcinogenic activity of ethinyl estrogens is determined by both their hormonal characteristics and their conversion to catechol metabolites
109. Conversion of estrone to 2- and 4-hydroxyestrone by hamster kidney and liver microsomes: Implications for the mechanism of estrogen-induced carcinogenesis
110. Functional role of estrogen metabolism in target cells: Review and perspectives
111. Estrogen-induced cell transformation and DNA adduct formation in cultured Syrian hamster embryo cells
112. Serum and tissue levels of estradiol during estrogen-induced renal tumorigenesis in the Syrian hamster
113. Induction of cathepsin D protein during estrogen carcinogenesis: Possible role in estrogen-mediated kidney tubular cell damage
114. Endogenous concentration and subcellular distribution of estrogens in normal and malignant breast tissue
115. The importance of local synthesis of estrogen within the breast
116. Prognostic value of breast cancer aromatase
117. Stromal spindle cells contain aromatase in human breast tumors
118. Detection of intratumoral aromatast in breast carcinomas
119. In situ aromatization enhances breast tumor estradiol levels and cellular proliferation
120. Estrogen-dependent kidney tumors
121. Estrogen carcinogenesis in hamster tissues: Role of metabolism
122. Induction of uterine adenocarcinoma in CD-1 mice by catechol estrogens
123. Metabolic aspects of estrogens in man
124. P450 enzymes of estrogen metabolism
125. Characterization of human microsomal cytochrome P450 enzymes
126. Estradiol metabolism by complementary deoxyribonucleic acid-expressed human cytochrome
127. Nature of cytochrome P450 involved in the 2/4-hydroxylation of estradiol in human liver microsomes
128. Cytochrome P450 metabolism of estrogen in hamster liver and kidney
129. 17β-Estradiol hydroxylation catalyzed by human cytochrome P450 1B1
130. Uterine adenocarcinoma in mice following developmental treatment with estrogens: A model for hormonal carcinogenesis
131. Mechanism of anterior pituitary tumor induction by oestrogen
132. 4-Hydroxylation of estradiol by human uterine myometrium and myoma microsomes: Implications for the mechanism of uterine tumorigenesis
133. 4-Hydroxylation of estrogens as marker of human mammary tumors
134. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on estrogen metabolism in MCF-7 breast cancer cells: Evidence for induction of a novel 17β-estradiol 4-hydroxylase
135. Mouse cytochrome P-450EF, representative of a new 1B subfamily of cytochrome P-450s: Cloning, sequence determination and tissue expression
136. Complete cDNA sequence of human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2
137. Gas chromatography/mass spectrometry of catecholestrogens
138. Cytochrome P-450-mediated redox cycling of estrogens
139. Temporary decrease in renal quinone reductase activity induced by chronic administration of estradiol to male Syrian hamsters
140. DNA damage caused by reactive oxygen species originating from a copper-dependent oxidation of the 2-hydroxy catechol of estradiol
141. Measurement of oxidative DNA damage by catechol estrogens and analogues in vitro
142. The quinone reductase gene: A unique estrogen receptor-regulated gene that is activated by antiestrogens
143. Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-α and estrogen receptor-β
144. Characterization of DNA damage induced by 3,4-estrone-o-quinone in human cells
145. An o-quinone form of estrogen produces free radicals in human breast cancer cells: Correlation with DNA damage
146. DNA single strand breaks in kidneys of Syrian hamsters treated with steroidal estrogens. Hormone-induced free radical damage preceding renal malignancy
147. Sex hormone-induced nuclear DNA damage and lipid peroxidation in the dorsolateral prostates of Noble rats
148. Microsome-mediated 8-hydroxylation of guanine bases of DNA by steroid estrogens: Correlation of DNA damage by free radicals with metabolic activation to quinones
149. Peroxidative in vitro metabolism of diethylstilbestrol induces formation of 8-hydroxy-2′-deoxyguanosine
150. Elevated 8-hydroxydeoxyguanosine levels in DNA of diethylstilbestrol-treated Syrian hamsters: Covalent DNA damage by free radicals generated by redox cycling of diethylstilbestrol
151. 8-Hydroxylation of guanine bases in kidney and liver DNA of hamsters treated with estradiol: Role of free radicals in estrogen-induced carcinogenesis
152. The etiology of breast cancer. Characteristic alteration in hydroxyl radical-induced DNA base lesions during oncogenesis with potential for evaluating incidence risk
153. The etiology and prediction of breast cancer
154. 3H]-hydride reduction
155. Target organ-specific inactivation of drug metabolizing enzymes in kidney of hamsters treated with estradiol
156. Induction by estrogens of lipid peroxidation and lipid peroxide-derived malonaldehyde-DNA adducts in male Syrian hamsters: Role of lipid peroxidation in estrogen-induced kidney carcinogenesis
157. Concentration dependence of pro-oxidant and antioxidant properties of catecholestrogens
158. Inhibition of estrogen-induced renal carcinoma in Syrian hamsters by vitamin C
159. Mechanism of inhibition of estrogen-induced renal carcinogenesis in male Syrian hamsters by vitamin C
160. Estrogen-induced endogenous DNA adduction: Possible mechanism of hormonal cancer
161. Lipid hydroperoxide-induced endogenous DNA adducts in hamsters: Possible mechanism of lipid hydroperoxide-mediated carcinogenesis
162. Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues
163. An estrogen-nucleic acid adduct. Electroreductive inter-molecular coupling of 3,4-estrone-o-quinone and adenine
164. Molecular characteristics of catechol estrogen quinones in reactions with deoxyribonucleosides
165. Molecular origin of cancer: Catechol estrogen-3,4-quinones as endogenous tumor initiators
166. 2-1-N3Ade adducts by reaction of E2-3,4-quinone with sDNA
167. Relating aromatic hydrocarbon-induced DNA adducts and c-Harvey-ras mutations in mouse skin papillomas: The role of apurinic sites
168. Mechanisms of tumor initiation by polycyclic aromatic hydrocarbons in mammals
169. Estrogen-nucleic acid adducts: Guanine is a major site for interaction between 3,4-estrone quinone and CO III gene
170. Mechanism of cytochrome P450-catalyzed aromatic hydroxylation of estrogens
171. Reaction of the Premarin® metabolite 4-hydroxyequliin semiquinone radical with 2′-deoxyguanosine: Formation of unusual cyclic adducts
172. Alkylation of 2′-deoxynucleosides and DNA by the Premarin® metabolite 4-hydroxyequilenin semiquinone radical
173. Formation of catechol estrogen adducts in kidneys of male hamsters treated with 4-hydroxyestradiol
174. 17β-Estradiol, diethylstilbestrol, Tamoxifen, Toremifene and ICI 164,384 induce morphological transformation and aneuploidy in cultured Syrian hamster embryo cells
175. Cytogenetic changes in renal neoplasms and during estrogen-induced carcinogenesis
176. Induction of chromosome aberrations in Syrian hamster renal cortical cells by various estrogens
177. Effects of estrogen on microtubule assembly: Significance for aneuploidy
178. Induction of micronucleation, spindle disturbance and mitotic arrest in human chorionic villi cells by 17β-estradiol, diethylstilbestrol and coumestrol
179. Effects of estrogenic chemicals on development
180. Aneuploidy of mouse cervicovaginal epithelium induced by perinatal estrogen treatment
181. Aneuploidy induction in human fibroblasts: Comparison with results in Syrian hamster fibroblasts
182. Alteration in diethylstilbestrol-induced mutagenicity and cell transformation by exogenous metabolic activation
183. Are diethylstilbestrol and estradiol mutagenic?
184. Mechanisms of gene inactivation by estrogens
185. Molecular mechanisms of gene inactivation by different mutagens
186. Induction by estrogens of methotrexate resistance in MCF-7 breast cancer cells
187. Estrogen-induced microsatellite DNA alterations are associated with Syrian hamster kidney tumorigenesis
188. Induction of microsatellite instability by oxidative DNA damage
189. Molecular genetics analysis of clear cell adenocarcinomas of the vagina associated and unassociated with diethylstilbestrol exposure in utero
190. Catecholestrogens as mediators of carcinogenesis: Correlation of aromatic hydroxylation of estradiol and its fluorinated analogs with tumor induction in Syrian hamsters
191. DNA adduct formation in liver and kidney of male Syrian hamsters treated with estrogen and/or α-naphthoflavone
192. Long-term toxicologic studies of 2,3,7,8-tetrachloro-p-dibenzodioxin in laboratory animals
193. Inhibition of 7,12-dimethylbenzanthracene-induced rat mammary tumor growth by 2,3,7,8-tetrachlorodibenzodioxin
194. Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin
195. Exposure to polychlorinated dibenzo-p-dioxins and -furans and breast cancer mortality in a cohort of female workers of a herbicide producing plant in Hamburg
196. Cancer mortality among workers in a chemical plant contaminated with dioxin
197. Carcinogenicity of TCDD: Experimental, mechanistic, and epidemiologic evidence
198. Interactions between hormones and chemicals in breast cancer
199. The role of the estrogen receptor in diethylstilbestrol toxicity
200. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice
201. An MMTV-Wnt-1 transgene induces mammary gland hyperplasia and tumorigenesis in mice lacking estrogen receptor-α