PHENOBARBITAL PROMOTES THE DEVELOPMENT OF ADENOCARCINOMAS IN THE ACCESSORY SEX GLANDS OF MNU-INOCULATED L-W RATS

Aged Lobund-Wistar (L-W) rats develop: (i) spontaneous and induced met astasizing adenocarcinomas in the prostate and seminal vesicle (P-SV) complex; and (ii) spontaneous hepatomas and hepatocarcinomas. Within t he time-frame of 14 months, similar adenocarcinomas were induced in th e P-SV complex in 70-90% of younger L-W rats by a single i,v, inoculat ion of methylnitrosourea (MNU) which was followed by slow release s,c. implants of testosterone propionate (TP). Within the same time-frame, neither MNU nor TP alone induced significant incidences of P-SV tumor s; and untreated control L-W rats were disease-free. Methylnitrosourea or TP and combinations thereof did not induce liver tumors. However, when MNU-inoculated L-W rats were fed phenobarbital (PB), they develop ed (i) metastasizing adenocarcinomas in the P-SV complex and (ii) alte red cellular foci and nodules in the livers. Methylnitrosourea induced a high incidence of benign lung adenomas which progressed to lung can cers in numbers which were of marginal significance. Thus, dormant MNU -initiated cells in the P-SV complex were activated by phenobarbital, to produce adenocarcinomas in that complex.