Effect of Hyperprolactinemia Induced by Prolactinoma (MtT/F84) on the Accessory Sexual Organs of Male Rat

A new transplantable prolactinoma, designated MtT/F84 has been serially passaged in female F344 rats. Persistently high levels of serum prolactin could be achieved in male F344 rats by MtT/F84 inoculating under the skin. This investigation deals with the effects of hyperprolactinemia upon the accessory sexual organs of male rats during puberty. The weights and the concentrations of dihydrotestosterone (DHT) in the dorsal prostate increased significantly in rats with moderate hyperprolactinemia (756 ± 179 ng/ml), but they in rats with marked hyperprolactinemia (3612 ± 1089 ng/ml) were similar t.o those of control rats. In contrast, serum testosterone levels (0.52 ± 0/17 ng/ml) in those of hyperprolactinemic rats were significantly decreased compared to that of controls (1.11± 0.13 ng/ml). These results suggested that the growth-promoting effect of prolactin on the rat prostate mediated through the action of androgen varied according to the degree of hyperprolactinemia

Metabolism of the α,β-Unsaturated Ketones, Chalcone and trans-4-Phenyl-3-buten-2-one, by Rat Liver Microsomes and Estrogenic Activity of the Metabolites

PBO was oxidized by cytochrome P450 1A1, 1A2, 2C6 and 2E1. Chalcone and PBO were negative in an estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, 4-hydroxychalcone, 2-hydroxychalcone, 4'-hydroxychalcone and 4-OH-PBO exhibited estrogenic activity. DMD #2634

Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid

Childhood radiation exposure is a known thyroid cancer risk factor. This study evaluated the effects of age on radiation-induced thyroid carcinogenesis in rats irradiated with 8 Gy X-rays. We analyzed cell proliferation, cell death, DNA damage response, and autophagy-related markers in 4-week-old (4W) and 7-month-old (7M) rats and the incidence of thyroid tumors in 4W, 4-month-old (4M), and 7M rats 18 months after irradiation. Cell death and DNA damage response were increased in 4W rats compared to those in controls at 1 month post-irradiation. More Ki-67-positive cells were observed in 4W rats at 12 months post-irradiation. Thyroid tumors were confirmed in 61.9% (13/21), 63.6% (7/11), and 33.3% (2/6) of irradiated 4W, 4M, and 7M rats, respectively, compared to 0%, 14.3% (1/7), and 16.7% (1/6) in the respective nonirradiated controls. There were 29, 9, and 2 tumors in irradiated 4W, 4M, and 7M rats, respectively. The expression of several autophagy components was downregulated in the area surrounding radiation-induced thyroid carcinomas in 4W and 7M rats. LC3 and p62 expression levels decreased in radiation-induced follicular carcinoma in 4W rats. Radiosensitive cells causing thyroid tumors may be more prevalent in young rats, and abrogation of autophagy may be associated with radiation-induced thyroid carcinogenesis

Induction of Cataract in Methylnitrosourea Treated Fischer (F344) Rats

Cataracts were observed in female F344 rats who intravenously received methylnitrosourea (MNU), a potent carcinogen for multiple organs, in one dose of 50 mg/kg body weight. Induction of cataract 40 weeks after MNU treatment was 41 % whereas no cataract was observed in control rats. The aggregation of βH-crystallin fraction by MNU was studied in vitro. HPLC pattern ofβH-crystallin changed when lens protein was incubated for 24 hrs with MNU. HPLC patterns indicated that MNU induced high molecular weight aggregates ofβH-crystallin. This study conveys some indication about the direct interaction of MNU with lens protein in cataract formation.This work was supported in part by Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan

Effect of 17 β-estradiol, Retinoic Acid and Tamoxifen upon Primary and Transplanted Thyroid Tumor in B5C3F1 Mice Fed an Iodine Deficient Diet

This study was aimed to establish TSH dependent, transplantable thyroid tumor (TT) in B6C3F1 (BCF1) mice. In addition, transplanted TT was examined for its growth in mice given 17β- estradiol (E2), retinoic acid (RA), tamoxifen (TAM), T3 and T4. Both sexes of BCF1 mice were observed for 12 months under IDD and distilled water (DW), starting at 4 weeks of age. Groups of mice received an i.p. injection of radioactive iodine (131I) once at a dose of 60 μ Ci/head and/or given 0.25 mg E2 pellet s.c. One piece of induced pituitary or thyroid tumor was individually dissected aseptically and s.c. grafted under the fat pad of one site of the neck in the same strain of mice at 5 weeks of age. All mice were sacrificed between 7.5 to 13.5 months after grafting the tumors depending on the experiments. The transplantability of both pituitary and thyroid tumor was 100% in IDD mice, but TT was about 50% with a combined treatment of IDD plus E2. A supplement of thyroid hormones of T3 or T4 in mice with IDD completely inhibited the growth of in situ or grafted thyroid tumors. The growth of in situ thyroid gland was significantly promoted by the oral administration of RA in both sexes, whereas the growth of transplanted TT was significantly increased by RA in the female, but not in the male. Oral administration of TAM proved inhibitory upon in in situ and transplanted TT in the male, but not in the female. Thyroid tumor induced by IDD could grow only in mice with IDD and was partially regulated of its growth by RA and TAM.A part of this work was supported by a grant-in-aid from the Ministry of Health and Welfare, Japan