Chemical Carcinogens Combined with Hormonal Stimulation of Cell Proliferation

Induction of prostatic adenocarcinomas by chemical carcinogens is rare. Only two organic chemical carcinogens, i.e., N-nitroso-bis-(oxopropyl)amine (BOP) and 3,2'-dimethyl-4-aminobiphenyl (DMAB), cause prostate adenocarcinomas upon systemic administration, without any additional concomitant or subsequent treatment [217, 218]. Direct application of chemical carcinogens to prostate tissue in experimental animals produces sarcomas or squamous cell carcinomas (see [5,219]).

Hormonal stimulation of cell proliferation in the prostate at the time of carcinogen administration has been demonstrated to increase the sensitivity of the target cells for tumor induction [199, 220-223]. Dorsolateral prostate adenocarcinomas have been produced at 5-25% incidence when prostatic cell proliferation was stimulated in combination with treatment with indirect-acting carcinogens, such as DMAB and 9,12-dimethylbenz[a]anthracene, and direct-acting chemical carcinogens, such as N-methyl-N-nitrosourea (MNU); except for DMAB, these carcinogens do not induce these tumors when administered alone [199,220- 223]. However, not in all studies has this enhancing effect of stimulation of prostatic cell proliferation on prostate carcinoma induction been found [197, 200, 224,225]. Nevertheless, stimulation of cell proliferation can be considered to be co-carcinogenic for prostate cancer induction in rats by many chemical carcinogens.

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