OROTIC-ACID ENHANCEMENT OF PRENEOPLASTIC AND NEOPLASTIC LESIONS INDUCED IN THE PANCREAS AND LIVER OF HAMSTERS BY N-NITROSO(2-HYDROXYPROPYL)(2-OXOPROPYL)AMINE

The effect of dietary erotic acid (OA) in liver-pancreas carcinogenesi s induced in female Syrian hamsters by N-Nitroso(2-hydroxypropyl) (2-o xopropyl)amine (HPOP) was evaluated. All animals infused with the carc inogen received the same doses. Results of the control group which rec eived no OA or carcinogen mere compared with the results of: (a) hamst ers treated with HPOP and fed a regular 20% protein synthetic diet (gr oup 1); (b) hamsters fed the OA diet for a brief time period during in itiation with the carcinogen (group 2); and (c) hamsters in which OA w as administered after carcinogen infusion for life (group 3). All anim als of the control group were normal at autopsy, while those in group 1 (HPOP alone) revealed the spectrum of lesions accepted as classical in the multistep hyperplasia-dysplasia-carcinoma in situ (CIS) sequenc e of carcinogenesis. Results of group 2, in light of group 1, revealed an increased incidence of the following lesions in the common pancrea tic duct: dilatation, 2.5 times; nat and papillary hyperplasia, 2 time s; and dysplasia (atypical hyperplasia), 12 times. No significant incr ease of CIS and invasive cancer in the body and tail of the pancreas w as observed; in addition, the incidence, nature, and location of pancr eatic adenocarcinomas mere not affected. Yet, the effect of OA adminis tered after carcinogen infusion (group 3) when compared to group 1 see med to enhance a further increase in the incidence of practically all lesions throughout the pancreas. An obvious overall step-up incidence along the multistep hyperplasia-dysplasia-CIS-invasive cancer process in the pancreas was observed. The increase in incidence of nat, papill ary, and atypia of the epithelium of the common pancreatic duct in gro up 3 was mild compared to that found in the same duct of group 2, but the increase in incidence of these same three lesions when found in th e main ducts mas marked: nat hyperplasia, 3-fold; papillary hyperplasi a, 2.5-fold; atypical hyperplasia, 3-fold. The increase in incidence o f CIS in this group was 5-fold and papillary adenocarcinomas, 3-fold, when compared to 5% found in groups 1 and 2. Hepatic malignancies (cho langiocarcinomas) occurred in 6% of the cases in group 3 compared to n one in group 2; the incidence of malignancy in the gallbladder was the same in groups 2 and 3 but three times greater than that in group 1. Our results suggest that not all ductal cells of the pancreas respond to OA promotion, which implies that various pancreatic tumors in the h amster, and by extrapolation, in humans, may have different etiologies .