Sex Hormone Dependency of Diethylnitrosamine‐induced Liver Tumors in Mice and Chemoprevention by Leuprorelin
Open Access
- 1 March 2001
- journal article
- Published by Wiley in Japanese Journal of Cancer Research
- Vol. 92 (3), 249-256
- https://doi.org/10.1111/j.1349-7006.2001.tb01089.x
Abstract
The prevalence of liver tumors throughout the world makes it imperative to seek chemopreventive agents. This tumor appears to be hormone-responsive and hormonal manipulations may therefore be beneficial. On this basis, both sexes of 12-day-old B6C3FJ mice were injected i.p. with diethylnitrosamine (DEN) at the dose of 2.5 μg/g body weight and observed for 32 weeks (males) or 36 weeks (females). In 100% of male mice, liver tumors were observed with an average diameter of 2.72 mm and multiplicity of 60.8. Orchidectomy at 6 weeks of age in these mice inhibited the incidence, multiplicity and size to 63%, 5.6 and 1.54 mm, respectively. By further implantation with an E2 pellet at monthly intervals, these parameters were reduced to 26%, 0.6 and 0.61 mm, respectively. Administration of a gonadotropin-blocking chemical, leuprorelin, to DEN-treated male mice significantly reduced the multiplicity and size of tumors to 18.3 and 2.54 mm (P<0.01 compared to those of DEN only). In female mice, the incidence of liver tumor was significantly smaller than that of males. However, ovariectomy and/or testosterone supplement significantly increased the occurrence of liver tumor. An anti-estrogen, toremifene, caused a marked further decrease of liver tumors. Mitotic indices with bromodeoxyuridine in tumor tissues paralleled the occurrence of liver tumors. Serum testosterone levels were significantly reduced by orchidectomy or by leuprorelin administration. These results further confirm that liver tumor is testosterone-responsive and hormonal manipulation by surgical orchidectomy or by chemical orchidectomy i.e. by leuprorelin, could substantially prevent the appearance of liver tumors.Keywords
This publication has 40 references indexed in Scilit:
- Heterogeneity in androgen receptor levels and growth response to dihydrotestosterone in sublines derived from human hepatocellular carcinoma line (KYN-1)Liver International, 2008
- Effects of castration and androgen replacement on tumour growth of human hepatocellular carcinoma in nude miceJournal of Hepatology, 1996
- Leuprolide Acetate Prevents Toxic Effects of Cisplatin on the Kidneys and Gastrointestinal Tract.Endocrine Journal, 1995
- Significance of Strain and Sex Differences in the Development of 252Cf Neutron‐induced Liver Tumors in MiceJapanese Journal of Cancer Research, 1992
- Hormonal treatment of hepatocellular carcinomaJournal of Hepatology, 1992
- Hepatocellular carcinomaDigestive Diseases and Sciences, 1991
- Hormonal manipulation of human hepatocellular carcinoma: A clinical investigative and therapeutic opportunityJournal of Hepatology, 1990
- Effect ofD-tryptophan-6-luteinizing hormone-releasing hormone on the tumoral growth and plasma sex steroid levels in cirrhotic patients with hepatocellular carcinomaHepatology, 1989
- Response to cyproterone acetate treatment in primary hepatocellular carcinoma is related to fall in free 5α-dihydrotestosteroneEuropean Journal of Cancer and Clinical Oncology, 1987
- Aflatoxin carcinogenesis: Inhibition of liver cancer induction in hypophysectomized ratsInternational Journal of Cancer, 1969