vitamin-a-acid-ethylamide and Neoplasms

Topics: Animals; Antineoplastic Agents; beta Carotene; Butylhydroxybutylnitrosamine; Carcinoma in Situ; Carcinoma, Papillary; Carotenoids; Cell Differentiation; Dose-Response Relationship, Drug; Epithelium; Fenretinide; Humans; Isotretinoin; Neoplasms; Neoplasms, Experimental; Tretinoin; Urinary Bladder Neoplasms; Vitamin A

Syrian hamsters were treated with either a low (10 mg/kg body weight) or high (40 mg/kg body weight) single dose of bis(2-oxopropyl)nitrosamine (BOP) and beginning 1 week later fed either low (0.2 mmol/kg diet) or high (0.4-1.0 mmol/kg diet) levels of one of four retinoids [13 cis retinoic acid (13-cis-RA), N-ethylretinamide (ERA), N-(2-hydroxyethyl)retinamide (OHERA) or N-(phenyl)retinamide (PRA)] for periods of 40 or 50 weeks. The high retinoid levels (0.4-1.0 mmol/kg diet) fed following the highest BOP treatment enhanced pancreatic carcinoma yields (average number/effective animal) in males fed all four retinoids, and in females fed ERA and 13-cis-RA. Enhanced adenoma yields were also seen in all groups when high retinoid levels were fed following 40 mg BOP/kg body weight. However, these retinoid levels caused an increased adenoma yield in male hamsters only and did not modify carcinoma yields when fed following 10 mg BOP/kg body weight. Similarly, tumor yields at extra-pancreatic sites were elevated in retinoid-fed hamsters of both sexes after 40 mg BOP/kg body weight and in males fed ERA and 13-cis-RA after 10 mg BOP/kg body weight when retinoids were given at the high levels (0.4-1.0 mmol/kg diet). Increased incidences of bile duct and liver tumors in particular were found in hamsters given 40 mg BOP/kg body weight. Consumption of retinoid levels of 0.4 mmol/kg diet and above was also associated with a high incidence of liver cell necrosis, ovarian cysts and ovarian hemorrhage. Retinoids (ERA, OHERA, and PRA) fed at the low level (0.2 mmol/kg diet) following the low BOP dose did not enhance carcinogenesis in the pancreas or at other sites and did not cause alterations in morphologic observations.

Topics: Animals; Body Weight; Cricetinae; Dose-Response Relationship, Drug; Female; Isomerism; Isotretinoin; Male; Mesocricetus; Neoplasms; Nitrosamines; Pancreatic Neoplasms; Sex Factors; Tretinoin