Selective sex-related modification of diethylnitrosamine-induced carcinogenesis in BALB/c mice by concomitant administration of butylated hydroxytoluene.

Tumor induction in BALB/c mice by diethylnitrosamine (DENA) was shown to be sex related. Female mice killed 13.5 months after DENA exposure generally had higher incidences of forestomach and lung tumors than did males and also had higher numbers of lung tumors per tumor-bearing mouse. Although neither sex developed stomach tumors spontaneously, males had higher incidences of spontaneous lung tumors than did females (45 vs. 26%). When butylated hydroxytoluene (BHT) was given concomitantly with DENA treatment, females had an increased survival (68 vs. 43%) and a reduced incidence of forestomach squamous cell carcinomas (77 vs. 100%) compared with females given DENA alone. No such protective effect on survival or on the occurrence of stomach tumors was seen in males given BHT and DENA or on lung tumorigenesis in either sex. In males, BHT given alone increased survival of treated mice over that of untreated controls, but it had no such effect on the females. The results of this study suggested an as yet unexplained hormonal influence and/or dependence for this BHT modification of DENA tumorigenesis.