Modifying role of partial hepatectomy and gonadectomy in ethylnitrosourea-induced hepatocarcinogenesis.

Abstract

Abstract The modifying effect of partial hepatectomy and gonadectomy upon carcinogenesis in general and hepatocarcinogenesis in particular has been evaluated in 6-week-old C57BL/6J × C3HeB/FeJ F1 mice. Ethylnitrosourea (60 µg/g body weight) was administered once after sham hepatectomy or 48 hr following partial hepatectomy at which time DNA synthesis in the regenerating liver was 30-fold higher than in the sham-hepatectomized mice. Six days later, one-half of the partially hepatectomized and one-half of the sham-operated mice were gonadectomized. Survivors were killed at 90 weeks of age. The incidence of tumors has been evaluated at all tissue sites. The sex hormonal environment of the hosts was assessed by histological evaluation of kidneys and adrenal glands. This evaluation showed that following gonadectomy, the morphology of the above tissues and consequently the hormonal environment shifted from that observed in the intact mice towards one characteristic of the opposite sex, assuming an intermediate state. Although primary tumors developed at several sites, partial hepatectomy and gonadectomy modified primarily the development of liver tumors. Thus, partial hepatectomy enhanced significantly hepatocarcinogenesis in male but not in female mice, resulting in an increased difference in the incidence of liver tumors between the two sexes. Gonadectomy of males abolished the enhancing effect of partial hepatectomy upon ethylnitrosourea hepatocarcinogenesis while ovariectomy potentiated development of liver tumors, leading to a similar incidence of liver tumors in both castrates. Modulating effects of hepatectomy and gonadectomy operated by influencing the incidence of benign rather than malignant liver tumors. The ovariectomy of partially hepatectomized females also enhanced kidney tumorigenesis. Data suggested that since enhancing effect of partial hepatectomy was associated with increased macromolecular (DNA) synthesis at the time of the administration of carcinogen initiation and the change of hormonal environment coincided with promoting phase of hepatocarcinogenesis, the respective conditions operated independently by two different mechanisms.