Base-line data in a carcinogen-susceptible first-generation hybrid strain of Syrian golden hamsters: F1D Alexander.

Base-line data in over 600 control animals of both sexes of the first-generation hybrid BIO F1D Alexander strain of Syrian golden hamsters are presented. They involve mortality, body weights, spontaneous tumor incidence, and incidence of nonneoplastic lesions. The results confirmed previously published data on smaller numbers of animals of this hamster strain. Spontaneous tumors with an incidence of more than 2% were limited to lymphomas (less than or equal to 6%), adrenocortical carcinomas (less than 8%), adrenal adenomas (9-14% in males; 3.5% in females), islet cell adenomas (less than 6%), and follicular adenomas of the thyroid gland (3.5% in females only). This low incidence of spontaneous tumors and the high survival rate (compared to those of hamsters from other sources), together with the previously established high susceptibility to tumor induction by carcinogen administration, render the F1D Alexander hamster an excellent animal model for lifetime carcinogenesis bioassays.

Subchronic cigarette smoke inhalation studies in inbred syrian golden hamsters that develop laryngeal carcinoma upon chronic exposure.

Inbred BIO 15.16 Syrian golden hamsters were exposed for 6-20 weeks to smoke from three types of experimental cigarettes. The incidence and severity of laryngeal hyperplasia increased in these hamsters, a few (2) laryngeal papillomas appeared, alveolar macrophages became more frequent and aggregated, and hyperplasia of terminal bronchiolar epithelium occurred. This subchronic response of hamsters to smoke markedly differed for the three types of cigarettes. Statistical evaluation of the data by log linear models proved these differences to be significant. At equal doses of smoke, the most severe response was caused by an all-tobacco cigarette. The weakest subchronic effects, next to those seen in the negative control group, were elicited by smoke from a cellulose-derived tobacco supplement. The effects of smoke from a 1:1 blend of the two smoking materials were intermediate. The severity of the subchronic response of the respiratory tract paralleled the extent of malignant transformations of the larynx previously observed in the same animal model with the same three types of cigarettes in chronic inhalation studies.

Cigarette smoke inhalation studies in inbred Syrian golden hamsters.

Invasive carcinoma of the larynx was induced in 36.8% of inbred Syrian golden hamsters from strain B10 15.16, susceptible to this type of cancer when exposed to smoke from reference filter cigarettes for 59-80 weeks. Nearly half the animals (47.4%) showed laryngeal cancer, including noninvasive carcinoma and carcinoma in situ, which occurred with daily smoke exposures (twice a day for 12 min each time, for 27 sec out of each min) 7 days a week at smoke concentrations of 22%. When the smoke concentration was reduced to 11%, the number of induced lesions was reduced proprotionately. When a portion of tobacco was replaced in the cigarettes by a tobacco supplement, Cytrel (a trademark of the Celanese Corp., Charlotte, N.C.), a reduction of carcinogenesis proportionate to the Cytrel content of the cigarette took place. Smoke from cigarettes containing only Cytrel and no tobacco induced no carcinomas under the conditions used. Other dose-related changes observed were laryngeal papillomas, laryngeal epithelial hyperplasia, tracheal epithelial hyperplasia, and metaplasia and accumulation of alveolar macrophages. Tar deposition in lungs and accumulation of alveolar macrophages. Tar deposition in lungs and larynges was determined in a separate study by means of a marker, decachlorobiphenyl, added to the cigarettes. Admixture of Cytrel to cigarettes reduced tar deposition in the respiratory tract, which paralleled the decrease in the incidence of laryngeal carcinoma. However, the amounts of tar deposited in the larynx when 100% Cytrel was smoked were still significant, even though no carcinomas were observed. Thus smoke from Cytrel tobacco supplement may be less carcinogenic than equal amounts of tobacco smoke.

Mouse skin assay of condensate from smoking products other than tobacco.

The biologic activity of a smoking product other than tobacco (Cytrel) was compaed with that of an American-type blend of cigarette tobaccos by application of the smoke condensate (SC) to shaved mouse skin. In 4 nonsimultaneous experiments, SC's from the former were equivalent or lower in tumorigenicity than equal doses of those from the latter, studied simultaneously and under identical conditions; this was true for widely varying doses of SC's, ranging from 35 to 246 mg nonaqueous condensate (NAC) administered to each mouse/week for 63-92 weeks. The response to SC from smoking products other than tobacco ranged from a complete lack of epidermoid carcinomas and papillomas at the lower doses to an incidence of lesions in 25.3% of the animals at the highest dose. The SC from a typical American blend of tobaccos caused skin lesions in 18.7-39.1% of the animals. SC from type 324 Cytrel, applied at the even higher dose of 365 mg/mouse/week, caused papillomas or carcinomas in only 22.0% of the animals, as compared with 39.1% of mice after adminstration of 245 mg SC from the American blend of cigarette tobacco; this was the highest dose that could be achieved with a test material containing nicotine. SC from a 1:1 blend of Cytrel with cigarette tobacco produced considerably fewer skin lesions at the lower dose levels than did SC from tobacco. At the lowest dose of 35 mg/mouse/week, 2 and 18.7% of the animals had lesions, and at a 54-mg dose, 11.3 and 22.7% had lesions from the blend and tobacco samples, respectively. At an increased level (113 mg), the response was the same for the SC from a 1:1 blend and from cigarette tobacco. There existed an excellent dose-response relationship for SC from type 308 Cytrel tested at four dose levels: 8.4, 113, 246, and 383 mg NAC/mouse/week, with 0, 18.7, 25.3, and 57.7% of the animals exhibiting skin lesions, respectively. Based on the criteria inherent in the technique of "mouse skin painting", Cytrel variants appeared to be lower or equal in tumorigenicity than did cigarette tobacco.