Effect of Nicotine and Cigarette Smoke on an Experimental Model of Intraepithelial Lesions and Pancreatic Adenocarcinoma Induced by 7,12-Dimethylbenzanthracene in Mice

Abstract

To evaluate the effects of nicotine and cigarette smoke exposure on mice submitted to 7,12-dimethylbenzanthracene (DMBA) model of pancreatic carcinogenesis. One hundred fourteen male mice were divided into the DMBA-n and DMBA-s groups: the DMBA-n group was given 2 mg/kg per dose of nicotine ([3-(1-methyl-2-pyrrolidinyl)pyridine]) subcutaneously for 45 days, and the DMBA-s group was exposed to 100 mg/m of cigarette smoke. At day 16, 1 mg of DMBA crystals was implanted in the pancreatic head of both groups. Euthanasia was performed in all mice 30 days after the surgery. The specimens were evaluated according to the following criteria: normal ducts, reactive hyperplasia, pancreatic intraepithelial neoplasm 3 (PanIN-3), and carcinoma. For statistical analysis, DMBA-exclusive ([DMBA-e] historical control group) was included. The frequency of PanIN in the 3 groups was almost the same when considering the higher-grade lesions: DMBA-e (16 [66.7%]), DMBA-s (20 [66.7%]), and DMBA-n (12 [44.4%]). Pancreatic adenocarcinoma has a higher frequency in the DMBA-n group (14 [51.9%]) than in the DMBA-e (4 [16.7%]) and DMBA-s (4, 13.3%) groups. The DMBA-s group has the highest score of PanIN-3 (40%). The differences among the groups were statistically significant (P = 0.05, Fisher exact test). Nicotine but not cigarette smoke promotes pancreatic DMBA carcinogenesis in mice. Pancreatic adenocarcinomas and PanINs have the same phenotypic appearance as those that occur in humans.