The effect of dietary orotic acid (OA) in liver-pancreas carcinogenesis induced in female Syrian hamsters by N-Nitroso(2-hydroxypropyl) (2-

The effect of dietary orotic acid (OA) in liver-pancreas carcinogenesis induced in female Syrian hamsters by N-Nitroso(2-hydroxypropyl) (2oxopropyl)amine (HPOP) was evaluated. All animals infused with the carcinogen received the same doses. ReSUlts of the control group which received no OA or carcinogen were compared with the results of: (a) hamsters treated with HPOP and fed a regular 20% proteIn synthetic diet (group 1); (b) hamsters fed the OA diet for a brief time period during initiation with the carcinogen (group 2); and (c) hamsters In which OA was administered after carcinogen infusion for life (group 3). All animals 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-dysplasla.cardnoma in situ (CIS) sequence ofcarclnogenesls. ResUlts ofgroup 2, in light ofgroup 1, revealed an increased Incidence of the following lesions in the common pancreatic duct: dilatation,2.5 times;flat and papifiaryhyperplasla,2 tImes;and dysplasla (atypical hyperplasia), 12 dmes No significant increase of CIS andinvasivecancerin thebodyandtailof thepancreaswasobserved;in addition, the Incidence, nature, and location of pancreatic adenocarcino. mas were not affected. Yet, the effect ofOA administered after carcinogen Infusion (group 3) when compared to group 1 seemed to enhance a further increase in the incidence ofpractically all lesions throughout the pancreas An obvious overall step-up incidence along the multistep hyperplasla dysplasla-CIS-invaslve cancer process in the pancreas was observed. The increase in incidence of flat, papillary, and atypla of the epithelium of the common pancreatic duct in group 3 was mild compared to that found in the same duct ofgroup 2, but the increase in incidence of these same three lesions when found in the main ducts was marked: flat hyperplasla, 3-fold; papillary hyperplasla, 2.5-fold; atypical hyperplasia, 3-fold. The increase in incidence of CIS in this group was 5-fold and papillary adenocarcino mas, 3-fold, when compared to 5% found In groups 1 and 2. Hepatic malignancies (cholanglocarcinomas) occurred In 6% of the cases in group 3 compared to none in group 2; the incidence of malignancy in the gallbladder was the same in groups 2 and 3 but three times greater than thatIngroup1.Ourresultssuggestthatnotallductalcellsofthe pancreas respond to OA promotion, which implies that various pancreatic tumors in the hamster, and by extrapolation, in humans, may have different etiologies.