Phenobarbital promotes multistage pulmonary carcinogenesis in MNU-inoculated L-W rats

Lobund-Wistar (L-W) rats develop adenocarcinomas spontaneously in the accessory sex glands (prostate-seminal vesicles) (P-SV) in the livers and in the lungs-all after long periods of latency. This report addresses (a) the multistage pattern of induced lung carcinomas in L-W rats and (b) the role(s) of two putative promotional agents (testosterone propionate (TP) and phenobarbital (PB) in the development of carcinomas in the lungs of L-W rats. Lung cancer is a rare slow-growing spontaneous neoplasm in L-W rats. Their incidence increased from 4.4% in avg 25.6 months (spontaneously) to 23.8% in avg 19 months following a single IV inoculation of methylnitrosourea (MNU), and further increased to 57% in avg 15 months by adding phenobarbital to the diet of MNU-inoculated rats. Three stages of lung tumorigenesis were manifested in L-W rats following treatments with MNU, or MNU + PB: hyperplasia, adenoma, and carcinoma.