Sex-Related Resistance in Hamsters to Adenovirus-12 Oncogenesis

Abstract

Summary Syrian hamsters (Mesocricatus auratus) were incoulated subcutaneously at birth with adenovirus-12, strain Huie. Thymectomy at 1 week of age resulted in essentially a twofold increase in tumor incidence in both sexes. However, tumor incidence remained higher in females than in males by a factor of 1.4 ± S.D. with a virus dose of 105.0 or 106.0 TCD50. Cortisone treatment begun at 1 week of age in hamsters given 106.3 TCD50 at birth and continued until a tumor developed or until the animals were 2 months of age increased tumor incidence by factors of 1.24 and 1.50 in females and males, respectively. However, tumor incidence in females still exceeded that in males by a factor of 1.3. Cortisone treatment begun at 3 weeks of age in hamsters given 106.3 TCD50 and continued at least 2 weeks after tumors developed or until death prior to or at 4 months of age resulted in equal tumor incidence, 95%, in both sexes; tumor incidence in control animals was 63% and 41% in females and males, respectively. Tumor regressions occurred in one-third of the hamsters of both sexes given 106.3 TCD50 at birth. Regressions were reduced to 3% in both sexes by continuous cortisone treatment, 2.5 mg weekly. Discontinuance of cortisone at the time tumors appeared or 2 or 4 weeks afterward resulted in 29 to 55% tumor regressions in males and 17 to 26% in females. Antibody responses to adenovirus-12 T-antigen as measured by complement-fixation and indirect immunofluorescence were depressed in thymectomized and cortisone-treated animals. Antibody responses in tumor-bearing animals, which were comparable to those of untreated animals, were detected beginning 10 days after cortisone was discontinued. These results revealed that the primary cell-virus interactions associated with adenovirus-12 oncogenesis occurred in virtually all animals given 106.3 TCD50. Secondary factors, such as the immunologic status of the host, determined whether transformed cells proliferated and continued to grow progressively as a tumor. Extensive steroid immunosuppression resulted in full expression of viral oncogeny. Restoration of the host's immunologic capacity by removing cortisone resulted in the succesful abortion of established tumors in a significant proportion of animals. The mechanism responsible for the greater incidence of tumors among normal or immunosuppressed females (excluding the extensively cortisonized animals) is yet to be clearly defined. Evidence is cited favoring a stimulatory role for estrogen.