azaserine and benzyl-acetate

Benzyl acetate was found to induce liver tumours and gastric squamous neoplasms in mice in a chronic bioassay conducted through the National Toxicology Program. An increased incidence of acinar cell adenomas of the pancreas of F344 rats was noted in the bioassay, but the significance of these lesions was confounded because the benzyl acetate was given by gavage in corn oil. The use of corn oil as a vehicle has been shown to enhance the growth of such lesions in the rat pancreas. The current studies were undertaken to evaluate benzyl acetate alone as an initiator and promoter of carcinogenesis in the pancreas. Alkaline elution analysis of acinar cell DNA showed no evidence of damage 1 hr after administration of benzyl acetate. Significant stimulation of growth of azaserine-induced foci was observed in a 6-month study, and a low but significant incidence of carcinoma in situ was observed in rats fed benzyl acetate in the diet for 2 yr. These experiments suggest that benzyl acetate is a weak promoter of the growth of carcinogen-induced and spontaneous pre-neoplastic foci in the pancreas.

Topics: Adenoma; Animals; Azaserine; Benzyl Compounds; Chi-Square Distribution; Corn Oil; DNA; Kidney; Kidney Failure, Chronic; Male; Pancreas; Pancreatic Neoplasms; Rats; Rats, Inbred F344

The response of LEW and F344 strain rats to the pancreatic carcinogen azaserine was compared using the size and number of azaserine-induced acidophilic acinar cell foci and nodules as parameters in a 4-month experiment. A second experiment compared the effect of corn oil intake by gavage and dietary routes on the growth of azaserine-induced pancreatic lesions in LEW rats. A third experiment tested the activity of benzyl acetate in regard to its ability to induce acinar cell foci or to promote the growth of such foci in azaserine-treated rats. The results showed that equivalent doses of azaserine induce two to seven times more foci in LEW than in F344 rats, and that LEW rats have a higher incidence of "spontaneous" foci than F344 rats. Azaserine-treated LEW rats that were given 5 mL corn oil/kg body weight 5 days per week by gavage developed more acinar cell foci than rats fed a basal diet (chow). Addition of an equivalent amount of corn oil to chow had a similar effect of enhancing the development of foci. Rats of neither strain developed acinar cell foci when benzyl acetate was given by gavage or in the diet nor was there evidence that benzyl acetate has a significant effect on the development of foci in azaserine-treated rats. These studies also demonstrate that the azaserine/rat model of pancreatic carcinogenesis which was developed in LEW rats can be adapted for use with F344 rats.

Topics: Animals; Azaserine; Benzyl Compounds; Corn Oil; Disease Models, Animal; Male; Pancreatic Neoplasms; Plant Oils; Rats; Rats, Inbred F344; Rats, Inbred Lew; Species Specificity