Liver Cancer: Neonatal Estrogen Enhances Induction by a Carcinogen

Weisburger, John H.; Yamamoto, R.; Korzis, J.; Weisburger, Elizabeth K.

doi:10.1126/science.154.3749.673

Cited by 12 publications

(5 citation statements)

References 8 publications

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“…Many investigators have shown that, in several strains of rats studied so far, liver of male rats was more susceptible to AAF and 2-diacetamidofluorene carcinogenesis than that of female rats (Bielschowsky, 1944;Firminger & Reuber, 1961;Kirby, 1947;Leathem, 1951;Morris & Firminger, 1956;Reuber, 1969;Symeonidis, 1954). Likewise N-hydroxy-AAF was shown to be more carcinogenic to the liver of male rat than that of the female (Miller et al 1961a;Weisburger, Yamamoto, Korzis & Weisburger, 1966). The results presented in this paper and those reported by DeBaun et al (1968) could explain the carcinogenicity data on the basis of differences in enzyme activities involved in esterification of the hydroxamic acid.…”

Section: Discussionmentioning

confidence: 99%

Effects of sex hormones on enzymic esterification of 2-(N-hydroxyacetamido)-fluorene by rat liver cytosol

Lotlikar

1970

Biochemical Journal

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1. Enzymic esterifications of 2-(N-hydroxyacetamido)fluorene and several other hydroxamic acids by liver cytosol were studied. Determination of 2-acetamido-3-methylthiofluorene was used for the assay. 2. With rat liver cytosol, requirement for ATP, Mg(2+) and SO(4) (2-) suggested formation of phosphate and sulphate esters of 2-(N-hydroxyacetamido)fluorene. 3. Rats showed sex and age differences in their activity. Liver from adult male rat was at least twice as active as liver from adult female rat. No such sex differences were found in mice, hamsters and guinea pigs. 4. Administration of testosterone (300mug/day) subcutaneously for 8 days increased the activity in the female rat by 100%, whereas diethylstilboestrol (100mug/day) had no effect. In the male rat diethylstilboestrol treatment decreased the activity by 60%, whereas testosterone pretreatment was without any effect. 5. Among various endocrine ablations such as adrenalectomy, castration, adrenalectomy-castration and hypophysectomy in the adult male rat, hypophysectomy was found to be the most effective in decreasing the activity of the liver to about 50% of control values. 6. Like 2-(N-hydroxyacetamido)fluorene, various other N-hydroxy derivatives of 2-acetamido-7-fluorofluorene, 2-acetamidophenanthrene, 4-acetamidobiphenyl and 4-acetamidostilbene were also shown to be esterified to different extents by rat liver cytosol.

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Section: Discussionmentioning

confidence: 99%

Effects of sex hormones on enzymic esterification of 2-(N-hydroxyacetamido)-fluorene by rat liver cytosol

Lotlikar

1970

Biochemical Journal

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“…Regardless of predisposing factors or geographic location, a striking sex disparity in the incidence of HCC has been consistently demonstrated, with men found to be 4 to 8 times more likely to develop the disease than women . It is from such epidemiologic observations that sex hormones were first surmised to modulate hepatocellular carcinogenesis nearly 5 decades ago . Since then, androgens and estrogens have been shown to mediate infectious hepatitis, hepatic fibrosis, NAFLD, and cirrhosis, in addition to HCC .…”

Section: Introductionmentioning

confidence: 99%

“…4 It is from such epidemiologic observations that sex hormones were first surmised to modulate hepatocellular carcinogenesis nearly 5 decades ago. 5,6 Since then, androgens and estrogens have been shown to mediate infectious hepatitis, 7,8 hepatic fibrosis, 9 NAFLD, 10 and cirrhosis, 11 in addition to HCC. 12 For example, androgens have been linked to hepatic tumorigenesis in mice models 13 and a predilection for HBV-related liver cancer in men.…”

Section: Introductionmentioning

confidence: 99%

Impact of sex on the survival of patients with hepatocellular carcinoma: A Surveillance, Epidemiology, and End Results analysis

Yang

Hanna

Usher

et al. 2014

Cancer

118

101

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BACKGROUND: Men are 4 to 8 times more likely to develop hepatocellular carcinoma (HCC) than women. Preclinical models have suggested a role for sex hormones in the development of HCC. In the current study, the authors investigated the impact of age, sex, race, and ethnicity on the survival of patients with HCC using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients diagnosed with HCC from 1988 through 2010 were identified from the SEER registry. Hazard ratios (HR) for overall survival (OS) were derived using the Cox regression model adjusted for race, year of diagnosis, marital status, treatment, birthplace, tumor differentiation, and tumor size. RESULTS: A total of 39,345 patients were identified; 76% were men and 34% were women (50% white, 12% African American, 21% Asian, 16% Hispanic, and 1% Native American). The median age at the time of diagnosis was 61 years for men and 67 years for women. Approximately 84% of patients had liver-limited disease and 16% had metastatic disease. Treatment information was available for patients diagnosed after 1998 (34,674 patients): 11% received liver-directed therapy, 11% underwent surgical resection, and 7% underwent liver transplantation. The HR for the OS of women versus men was 0.83 (95% confidence interval [95% CI], 0.77-0.88) for patients aged <55 years. The protective effect of sex on OS was found to be greatest in patients aged 18 to 44 years (HR, 0.75; 95% CI,), especially those with surgically resected tumors (HR, 0.68; 95% CI,) and those who were African American (HR, 0.85; 95% CI, 0.78-0.92 [P<.001]). There was no survival difference between sexes noted among Hispanics or patients aged >65 years. CONCLUSIONS: Sex appears to be associated with survival in patients with HCC. The role of androgens and estrogens in the development and progression of HCC warrants further investigation.

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“…implicated in carcinogenesis (Abell and Heidel-The response sf chemically induced temmors to elements of endocrine control has been well documented (Bao 1962;Lotlikar et al 1964;Weisburger et al 1966), but attempts to decipher the mechanisms involved have revealed an extremely complex situation. One area in which carcinogens and ste.roids do appear to play interrelated roles is in their interaction with the cytssol binding proteins involved in metabolism of steroid hormones and detoxification of xenobiotics (Smith et al 1977).…”

Section: Introductionmentioning

confidence: 99%

Influence of adrenalectomy and sex on the binding of 3-methylcholanthrene to cytosol macromolecules of rat liver

Bigger¹,

Ce²

1979

Can. J. Physiol. Pharmacol.

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Liver Cancer: Neonatal Estrogen Enhances Induction by a Carcinogen

Cited by 12 publications

References 8 publications

Effects of sex hormones on enzymic esterification of 2-(N-hydroxyacetamido)-fluorene by rat liver cytosol

Effects of sex hormones on enzymic esterification of 2-(N-hydroxyacetamido)-fluorene by rat liver cytosol

Impact of sex on the survival of patients with hepatocellular carcinoma: A Surveillance, Epidemiology, and End Results analysis

Influence of adrenalectomy and sex on the binding of 3-methylcholanthrene to cytosol macromolecules of rat liver

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