Effects of Androgens on Prostate Cancer Induction by Cadmium and Ionizing Radiation

Cadmium can be carcinogenic for the rat ventral prostate as demonstrated by Waalkes and co-workers [227, 228]. The selective sensitivity of the ventral prostate lobe for the carcinogenic action of cadmium is most likely due to the lack of cadmium-binding proteins in this lobe [229]. A single injection of cadmium chloride produced early stage carcinomas in the ventral lobe, but only when cadmium-induced testicular toxicity was avoided, either by keeping the cadmium dose low or by antagonizing the testicular toxicity of cadmium by simultaneous administration of zinc. These observations indicate that cadmium induces proliferative lesions in the rat ventral prostate only when testicular function, conceivably testosterone production, is intact. In addition, these data suggest that androgens also act as tumor promotors in this system, but this hypothesis has not been tested. Other mechanisms may also be involved, because, for example, testosterone considerably increases disposition and retention of cadmium in the rat ventral prostate [230].

Local radiation (X-ray) exposure of the pelvis has been shown to induce prostate carcinomas in mice [231] and rats [232]. Prostate carcinomas (33 % incidence) developed only in rats that were castrated and received androgen-replacement prior to irradiation, whereas intact and castrated rats did not develop prostate cancer following irradiation. These observations suggest that testosterone treatment was required for tumor development, perhaps as tumor promotor [232].

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