RESUMO
Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with 3H-methyltrienolone as the ligand. Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P less than 0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P less than 0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations. Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.
Assuntos
Neoplasias do Colo/análise , Receptores Androgênicos/análise , Animais , Azoximetano/farmacologia , Sítios de Ligação , Peso Corporal/efeitos dos fármacos , Colo/metabolismo , Neoplasias do Colo/induzido quimicamente , Ciproterona/análogos & derivados , Ciproterona/farmacologia , Acetato de Ciproterona , Citosol/metabolismo , Estrenos/metabolismo , Cinética , Masculino , Metribolona , Orquiectomia , Ratos , Ratos Endogâmicos , Neoplasias Retais/análise , Testosterona/farmacologiaRESUMO
Primary xenotransplantation of six different human colorectal adenocarcinomas onto nude mice yielded a mean tumor take of 85%. Administration of steroid hormones induced tumor remissions in some cases. Neither the stage of the original patient's tumors nor their hormone receptor content seemed to be related to the result of the hormone therapies. It is concluded that some colorectal cancers can be treated as hormone-sensitive tumors.
Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Hormônios/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Adenocarcinoma/patologia , Animais , Neoplasias do Colo/patologia , Di-Hidrotestosterona/uso terapêutico , Estradiol/uso terapêutico , Feminino , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Progesterona/uso terapêutico , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Neoplasias Retais/patologia , Transplante HeterólogoRESUMO
The effects of androgens on colon carcinogenesis were studied in 90 male Fisher-344 rats, given 10 weekly subcutaneous (SC) injections of 7.5 mg azoxymethane (AOM)/kg body weight, starting at 12 weeks of age. Thirty rats received the AOM course only (AOM only). Thirty rats were gonadectomized at 10 weeks of age and underwent the AOM course (castrated). In 30 additional castrated rats, hormone substitution was achieved by sc injection of 1 mg dehydrotestosterone (DHT) three times a week for 12 weeks. AOM was given concommitantly, starting at 12 weeks of age (castrated and hormone substituted). Animals were sacrificed 25 weeks after first AOM injection. As assessed by weekly body weight data and periodic serum determinations of carcinoembryonic antigen (CEA), castrated animals showed a delayed onset of colonic carcinogenesis, compared to AOM-only-treated and hormone-substituted animals. Castration resulted in a decrease of mean tumor size as well as overall incidence of colonic tumors, compared to that observed AOM-only and castrated and hormone-substituted group, respectively (27 vs 47 vs 53%). Castration also resulted in lower mean serum CEA levels at the end of experiment than in the AOM-only and castrated and hormone-substituted group. These findings suggest a promoting effect of androgens in colon carcinogenesis.