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Investigation of a mechanism for Leydig cell tumorigenesis by linuron in rats


, : Investigation of a mechanism for Leydig cell tumorigenesis by linuron in rats. Toxicology and Applied Pharmacology 119(2): 195-204

In a previously conducted 2-year study, a concentration-dependent increase in Leydig cell adenomas was observed in Crl:CD BR (CD) rats fed diets containing the herbicide linuron. Linuron has been shown to be negative in a battery of six tests for genotoxicity; therefore, a nongenotoxic mechanism of tumorgenesis was investigated. Linuron is structurally related to the nonsteroidal antiandrogen, flutamide. Flutamide has also been shown to produce Leydig cell tumors within 1 year, presumably due to sustained hypersecretion of luteinizing hormone (LH) which occurs following disruption of the hypothalamic-pituitary-testicular (HPT) axis. To investigate whether linuron possesses antiandrogenic activity, sexually immature and mature CD rats were administered either 200 mg/kg linuron or 10 mg/kg flutamide (positive control) for 2 weeks. Accessory sex organs were weighed and serum hormone levels were measured to assess androgen status and alterations in the HPT axis. Serum from a multigeneration reproduction study with linuron was also analyzed for serum hormone levels. In addition, competitive receptor binding studies were conducted to evaluate the ability of linuron to bind to the androgen receptor. Linuron decreased accessory sex organ weights in sexually immature and mature linuron-treated rats. Increased serum estradiol and LH levels were observed in sexually mature linuron-treated rats. Serum estradiol and LH levels were also elevated in P-1 and F-1 male rats from the multigeneration reproduction study. These accessory sex organ and hormonal changes are consistent with those seen with the antiandrogen flutamide, the only exception being serum testosterone, which was elevated following exposure to flutamide but not to linuron. The inability of linuron to increase testosterone levels may reflect the lower potency of linuron as an antiandrogen compared with that of flutamide, which is a potent antiandrogen. Additionally, linuron competed with (3H)testosterone for binding to the androgen receptor. The IC-50 data for competition to the androgen receptor suggest that linuron is approximately 3.5 times less potent than flutamide. These data are consistent with the effects seen with flutamide and demonstrate that linuron is a less potent antiandrogen than flutamide. Collectively, these data support the hypothesis that linuron produces Leydig cell tumors via an antiandrogenic mechanism where sustained hypersecretion of LH appears to be responsible for the development of Leydig cell hyperplasia and adenomas.

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Accession: 002416746

PMID: 8480329

DOI: 10.1006/taap.1993.1060

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Nechaeva, A.S.; Vargina, A.K., 1956: Antigen accumulation by Flexner dysentery bacteria when cultivated with aeration. It was established that the process of antigen accumulation by dysentery bacteria occurs during the whole period of cultivation (24 hours), while in typhoid cultures this process terminates after 16-18 hours. Immunogenic activity of antigens was c...

Tauzin Fin P.; Crozat P.; Ragot P.; Sabathie M., 1985: Long term bladder drainage in surgical intensive care units. Long time bladder drainage in intensive care units is generally admitted as a very simple procedure, since there is a lot of indications. But this procedure gives two major complications. Nosocomial urinary tract infections appear to be responsibl...

Anonymous, 1986: Bioassays and other special techniques for plant hormones and plant growth regulators. A preliminary purpose of this multi-author handbook has been to assemble information on time-proven and new methods of detecting and characterizing growth regulators. The ten chapters are entitled: 1. Bioassays for plant hormones and growth regula...

de Vos, W.M.; Voorhorst, W.G.; Dijkgraaf, M.; Kluskens, L.D.; Van der Oost, J.; Siezen, R.J., 2001: Purification, characterization, and molecular modeling of pyrolysin and other extracellular thermostable serine proteases from hyperthermophilic microorganisms. Methods in Enzymology 330: 383-393

Karita, K.; Nakao, M.; Ohwaki, K.; Yamanouchi, Y.; Nishikitani, M.; Nomura, K.; Sato, M.; Yano, E., 2005: Blood lead and erythrocyte protoporphyrin levels in association with smoking and personal hygienic behaviour among lead exposed workers. Aims: To investigate the effects of smoking and personal hygienic behaviour on blood lead (BPb) and free erythrocyte protoporphyrin levels (FEP) in lead exposed workers.Methods: Subjects were 105 lead exposed male workers in a battery recycling pl...

Nakagami, Y.; Saito, H.; Matsuki, N., 1996: Optical recording of trisynaptic pathway in rat hippocampal slices with a voltage-sensitive dye. Society for Neuroscience Abstracts 22(1-3): 1519

Jahn, V., 1970: A nurse at 16?. Schwestern Revue 8(5): 10-11

Wierzbowska, A.; Robak, T.; Pluta, A.; Wawrzyniak, E.; Cebula, B.; Hołowiecki, J.; Kyrcz-Krzemień, Sławomira.; Grosicki, S.; Giebel, S.; Skotnicki, A.B.; Piatkowska-Jakubas, B.; Kuliczkowski, K.; Kiełbiński, M.; Zawilska, K.; Kłoczko, J.; Wrzesień-Kuś, A., 2007: Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Objectives: Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine ( FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukem...

Norris, J.A.; Garinger, G.; Kurtz, N.C., 1980: Selected recent court decisions. American Journal of Law & Medicine 5(4): 353-360

Tragl, K.H.; Kinast, H.; Steininger, H.; Geyer, G., 1978: Effect of in vivo administration of somatostatin on cell-free protein synthesis of pituitary and of adrenal ribosomes. Metabolism: Clinical and Experimental 27(9 Suppl 1): 1387-1390