Our recent study showed that nasal and paranasal (NPN) cavity tumors induced by N-nitrosobis(2-oxopropyl)amine (BOP) could be prevented by bilateral orchiectomy performed one week prior to weekly subcutaneous administration of BOP. Castration did not affect tumor patterns in other BOP target tissues, except for those of the prostate. The sex hormone-dependency of these induced NPN tumors was recently evidenced by demonstration of testosterone receptors (TR) in these lesions, but not in normal NPN mucosa, indicating that TR are acquired during neogenesis. Epidemiological studies also point to a sex hormone-dependency of NPN tumors in man, based on a male predominance in their development. The sex hormone-dependency of NPN tumors, which are clinically characterized by their late diagnosis, unfavorable prognosis and limited effectiveness of therapeutic efforts, may open a new means for treatment of this disease. However, studies are needed to answer the following questions: 1) Can castration inhibit the growth (or cause regression) of induced NPN tumors? If the answer is yes, 2) at which stage of tumor development is testosterone withdrawal therapeutically effective? 3) Is the therapeutic effect of testosterone withdrawal therapeutically effective? 3) Is the therapeutic effect of testosterone withdrawal tumor-type specific, i.e., influences papillomas, squamous cell carcinomas and/or adenocarcinomas? We propose to use two groups of male rats. One group (Group 1) will be treated with BOP weekly for either 20 weeks (Group 1a), 30 weeks (Group 1b) or 40 weeks (Group 1c), with no further treatment after each of the 3 assigned treatment times. One-half of the rats in each subgroup will be sacrificed at the end of each treatment period and the other half will be allowed to die spontaneously. The second group (Group 2) will be treated similarly, with the exception that bilateral orchiectomies will be performed ater each of the 3 treatment periods (Groups 2a, 2b and 2c). As in group 1 each subgroup will be composed of 30 rats. The morphologic pattern, distribution and possibly the number of induced NPN lesions according to their histologic types will be recorded and the presence of TR will be sought. The serum testosterone level will be determined in animals of both groups. The data, including survival rates, will be analyzed statistically.
| Kazakoff, K; Iversen, P; Lawson, T et al. (1994) Involvement of cytochrome P450 2E1-like isoform in the activation of N-nitrosobis(2-oxopropyl)amine in the rat nasal mucosa. Eur J Cancer B Oral Oncol 30B:179-85 |
| Lawson, T A (1990) Activation of N-nitrosobis(2-oxopropyl)amine by liver and nasal mucosa tissue from intact and castrated male rats. Cancer Lett 53:39-43 |
| Pour, P M; Kazakoff, K (1989) Prevention of rectal cancer induced by N-nitrosobis(2-oxopropyl)-amine by exogenous testosterone in MRC rats. Carcinogenesis 10:2015-7 |
| Pour, P M; Stepan, K R (1988) The role of testosterone in the nasal cavity tumors induced by N-nitrosobis(2-oxopropyl)amine in rats. Carcinogenesis 9:1417-20 |
