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 orotic acid (OA) in liver-pancreas carcinogenesis induced in female Syrian hamsters by N-Nitroso(2-hydroxypropyl) (2-oxopropyl)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-dysplasia-carcinoma in situ (CIS) sequence of carcinogenesis. Results of group 2, in light of group 1, revealed an increased incidence of the following lesions in the common pancreatic duct: dilatation, 2.5 times; flat and papillary hyperplasia, 2 times; and dysplasia (atypical hyperplasia), 12 times. No significant increase of CIS and invasive cancer in the body and tail of the pancreas was observed; in addition, the incidence, nature, and location of pancreatic adenocarcinomas were not affected. Yet, the effect of OA administered after carcinogen infusion (group 3) when compared to group 1 seemed 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 flat, papillary, and atypia of the epithelium of the common pancreatic duct in group 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 the main ducts was marked: flat hyperplasia, 3-fold; papillary hyperplasia, 2.5-fold; atypical hyperplasia, 3-fold. The increase in incidence of CIS in this group was 5-fold and papillary adenocarcinomas, 3-fold, when compared to 5% found in groups 1 and 2. Hepatic malignancies (cholangiocarcinomas) 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 that in group 1.(ABSTRACT TRUNCATED AT 400 WORDS)
Kokkinakis
D M
DM
Department of Neurology, University of Texas Southwestern Medical Center at Dallas 75235-9036.
Albores-Saavedra
J
J
D000818:Animals; D002273:Carcinogens; D018281:Cholangiocarcinoma / Q000139:chemically induced* / Q000473:pathology; D006224:Cricetinae; D004357:Drug Synergism; D005260:Female; D005706:Gallbladder Neoplasms / Q000139:chemically induced* / Q000473:pathology; D006965:Hyperplasia / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008647:Mesocricetus; D009602:Nitrosamines; D009963:Orotic Acid; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens; D009602:Nitrosamines; C013624:N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine; D009963:Orotic Acid