vitamin-a-acid-ethylamide and Body-Weight

The long-term effects of N-ethylretinamide (NER) on the haematology of the rat, and the dose-related effects of retinoids on lymphoid organs of the mouse and rat were investigated. Retinoid-induced long-bone changes were used to develop a method for quantifying skeletal effects. This technique was used to investigate the activity of five retinamides in inducing long-bone changes in the rat. The ability of non-steroidal anti-inflammatory compounds (NSAICs) to prevent retinoid-induced skeletal effects was examined, and preliminary investigations made into the mechanisms of retinoid-induced long-bone remodelling. NER-fed rats had reduced red blood cell counts and fibrinogen values. Retinoids caused dose-related proliferation of the spleen and lymph nodes in the mouse and to a lesser extent in the rat. They induced dose-related reductions in femoral diaphysis and medullary cavity diameters in both rats and mice. Aspirin prevented NER-induced changes of rat long bones, but subsequent studies indicated this effect may be closely dependent on the dose level of both the retinoid and NSAIC administered. Retinoids induce rapid long-bone remodelling in the rat which tends to revert on feeding a control diet, but remodelling processes are different in the young growing rat and the mature animal.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood; Body Weight; Bone and Bones; Dose-Response Relationship, Drug; Female; Femur; Lymphoid Tissue; Mice; Mice, Inbred Strains; Organ Size; Rats; Rats, Inbred F344; Retinoids; Species Specificity; Tretinoin

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

The failure of N-ethylretinamide and N-(2-hydroxyethyl)retinamide to inhibit the incidence or severity of bladder carcinoma in female Fischer rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide supports the concept that the inhibition of bladder carcinogenesis by natural and synthetic retinoids is carcinogen-class specific.

Topics: Animals; Body Weight; FANFT; Female; Neoplasms, Experimental; Rats; Rats, Inbred F344; Thiazoles; Tretinoin; Urinary Bladder Neoplasms