The effects of estrogen on single dose dimethylnitrosamine carcinogenesis in male inbred Crl/CDF rats

The effect of longterm estrogen treatment (estradiol valerate) on male rats injected i.p. once with dimethylnitrosamine (DMN, 30 mg/kg, with protein starvation), was studied in 167 male inbred Crl/CDF rats. DMN was given at 40 days (immature rats) or at 90 days (mature rats) to investigate the action of carcinogen and hormone at different stages of development. Estrogen reduced life expectancy of male animals, and was associated with greatly increased breast tumour incidence (to 30%) compared with controls (3%, p less than 0.01). DMN alone enhanced lung tumorigenesis (p less than 0.001) and chronic estrogen treatment significantly reduced both the incidence and multiplicity of DMN-induced lung tumours in male rats (p less than 0.001). Also, estrogen treatment lowered the incidence of spontaneous lung tumours (p less than 0.005). The higher incidence of animals with kidney tubular adenomas and carcinomas induced by DMN in both mature and immature rats was statistically significant (p less than 0.001), but estrogen and the age at carcinogen treatment had no effect. Lethal mesenchymal kidney tumours developed in immature rats exposed to DMN (p less than 0.001), but only developed in mature DMN-treated rats if they received estrogen as well.