Abstract
The objective of this investigation was to elucidate the role of sex hormones in the progression and subsequent hormone dependency of mammary carcinomas induced by single or multiple administration of 7, 12-dimethylbenz[a]anthracene (DMBA). Ten milligrams of DMBA were administrated orally to female Sprague-Dawley (SD) rats once at the age of 42 days (Group A) and three times at the ages of 28, 42 and 56 days (Group B). All 70-day-old rats in Groups A and B were divided into 4 groups (I, II, III and IV), respectively. Rats in Groups I of A and B were intact controls. Rats in Groups II of A and B were ovariectomized (OVEX) at the age of 70 days. Rats in Group II of Group A and in Groups III of Groups A and B were divided into 4 subgroups (Group II-1, II-2, II-3 and II-4) and 3 subgroups (Group III-1, III-2 and III-3), respectively. Rats in Groups II-2 of A and III-1 of A and B, rats in Groups II-3 of A and III-2 of A and B and rats in Groups II-4 of A and III-3 of A and B were given injections of 0.01, 0.1 and 1 mg 17β-estradiol (E2), respectively. Rats in Groups IV of A and B were given injections of 4 mg progesterone (P). Injections of E2 or P were given 3 times a week between the ages of 70 and 217 days in Group A and the ages of 70 and 105 days in Group B. In Group A, there was no difference of incidence of mammary carcinomas among Groups I, II-2, II-4, III-1 and IV but the incidence of mammary carcinomas in Groups II-1, II-3, III-2 and III-3 was extremely low, compared with that in Group I. In Group B, a large number of mammary carcinomas developed and although there was no difference in the incidence of mammary carcinomas among Groups I, II, III and IV, the number of mammary carcinomas per rat decreased in Groups II, III-2 and III-3, compared with Group I. These findings indicate that the progression of mammary carcinomas induced by a single or multiple administration of DMBA was suppressed in ovariectomized rats and in rats with injections of high doses of E2. DMBA-induced mammary carcinomas in Group B were transplanted into OVEX rats (R-1), OVEX rats with injections of 0.01 mg E2 (R-2) and OVEX rats with injections of 1 mg E2 (R-3). According to tumorigenesis in those rats with various hormonal treatments (R-1, 2, 3), mammary carcinomas were classified into one of the four categories (Type A, B, C and D). Type A tumor: tumor developed greatly in R-2 but slightly or not in R-1 and R-3. Type B tumor: tumors developed greatly in R-1 but slightly or not in R-2 and R-3. Type C tumor: tumors developed greatly in R-3 but slightly or not in R-1 and R-2. Type D tumor: tumors developed greatly in R-1, R-2 and R-3. In Group B, rates of type A, B, C, D tumor were 43.2, 13.5, 24.3 and 18.9% in Group I, 26.3, 10.5, 21.1 and 42.1% in Group II, 40.0, 5.0, 45.0 and 10.0% in Group III-1, 38.5, 15.4, 30.8 and 15.4% in Group III-2, 28.6, 0, 71.4 and 0% in Group III-3 and 44.4, 33.3, 11.1 and 11.1 in Group IV, respectively. These results suggested that the hormonal status of the development process may be one of factors which affects the characteristics of hormone dependency and the multiple administration of DMBA may induce large numbers of carcinoma cells with varying dependency on hormones and carcinoma cells may be selected in hormonal conditions during progression.
