Lack of inhibition by retinoids of bis(2-oxopropyl)nitrosamine-induced carcinogenesis in Syrian hamsters.
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.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D007536:Isomerism; D015474:Isotretinoin; D008297:Male; D008647:Mesocricetus; D009369:Neoplasms / Q000139:chemically induced*; D009602:Nitrosamines / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000139:chemically induced; D012737:Sex Factors; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology*
D009602:Nitrosamines; C009675:vitamin A acid ethylamide; C022147:N-(2-hydroxyethyl)retinamide; C039375:N-phenylretinamide; D014212:Tretinoin; C013622:nitrosobis(2-oxopropyl)amine; D015474:Isotretinoin