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 metastasizing adenocarcinomas in the prostate and seminal vesicle (P-SV) complex; and (ii) spontaneous hepatomas and hepatocarcinomas. Within the time-frame of 14 months, similar adenocarcinomas were induced in the P-SV complex in 70-90% of younger L-W rats by a single i.v. inoculation 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 tumors; 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 developed (i) metastasizing adenocarcinomas in the P-SV complex and (ii) altered cellular foci and nodules in the livers. Methylnitrosourea induced a high incidence of benign lung adenomas which progressed to lung cancers 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.
Pollard
M
M
Lobund Laboratory, University of Notre Dame, IN 46556, USA.
Luckert
P H
PH
Scheu
J
J
D000008:Abdominal Neoplasms / Q000139:chemically induced / Q000473:pathology; D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology / Q000556:secondary; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000375:Aging; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004343:Drug Implants; D005834:Genital Neoplasms, Male / Q000139:chemically induced* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000556:secondary; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity*; D010534:Peritoneal Neoplasms / Q000139:chemically induced / Q000473:pathology; D010634:Phenobarbital / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology
D002273:Carcinogens; D004343:Drug Implants; D013739:Testosterone; D008770:Methylnitrosourea; D010634:Phenobarbital