Promoting effect of arachidonic acid supplementation on N-methyl-N-nitrosourea-induced pancreatic acinar cell hyperplasia in young Lewis rats

Abstract

Abstract. Arachidonic acid (AA) is naturally found in human breast milk. AA, together with docosahexaenoic acid, is commonly added as a functional food ingredient to commercial infant formula worldwide, in accordance with the international standard of Codex Alimentarius. However, few studies have been performed that are concerned with the possible carcinogenic effects of AA supplementation during neonatal life. The effect of dietary AA supplementation in dams, during gestation and lactation, was investigated in N-methyl-N-nitrosourea (MNU)-induced preneoplastic lesions in the exocrine pancreas of young Lewis rats. Dams were fed either an AA (2.0% AA) or a basal (<0.01% AA) diet. On postnatal day 0 (at birth), male and female pups received a single intraperitoneal injection of either 35 mg/kg MNU or vehicle. The morphology and proliferating activity of the exocrine pancreas were examined by proliferative cell nuclear antigen immunohistochemistry 7, 14, 21, 28 and/or 60 days post-MNU. Histopathologically, acinar cell hyperplasia (ACH) occurred in the MNU-treated groups 60 days after MNU injection, irrespecitive of whether the rats had been fed an AA diet. Morphometrically, the number and area of ACH per 1 mm 2 in MNU-treated rats increased significantly in the AA diet-fed rats, compared with basal diet-fed rats. The number of proliferative cell nuclear antigenpositive acinar cells in both the normal and hyperplastic areas of MNU-treated rats increased significantly in the AA diet-fed rats. In conclusion, providing dams with an AA-rich diet during gestation and lactation promotes MNU-induced pancreatic ACH in young Lewis rats.

Arachidonic acid supplementation does not affect N-methyl-N-nitrosourea-induced renal preneoplastic lesions in young Lewis rats

“…As in the previous study, the AA-supplemented diet was formulated by CLEA Japan (5,15). AA was purchased from Cargill Alking Bioengineering (Wuhan and Hubei, China).…”

“…N -methyl- N -nitrosourea (MNU), a direct-acting alkylating agent that interacts with DNA, is toxic and carcinogenic to the breast and pancreas as well as the immune, hematopoietic, reproductive, dental, gastrointestinal, nervous and sensory systems (3–5). Nitrosourea compounds including MNU have carcinogenic potency in the kidney of rats (6–8), and MNU induces mesenchymal tumors and nephroblastomas in rats (9,10).…”

“…Omega-3 fatty acids, such as docosahexaenoic acid, affect the growth of several cancers (14) and AA has been reported to affect carcinogenesis in certain organs. AA promotes the growth of tumors from an orthotopically transplanted breast cancer cell line (KPL-1) in female athymic BALB/c mice, urinary bladder tumors in a medium-term multi-organ rat carcinogenesis study (15), and preneoplastic lesions of the exocrine pancreas in an MNU-treated rat model (5). AA metabolites and enzymes are associated with renal tumors and related disease; cyclooxygennase-2 expression is associated with renal carcinoma (16,17), and prostaglandin E2 is associated with paraneoplastic hypercalcemia in nephroblastoma (18,19).…”

Proceedings of the 2013 Joint JSTP/NTP Satellite Symposium

“…After presentation of the results of the IHC analyses and from the criteria for proliferative lesions of pancreatic ducts 16 , 17 , 18 , most audience members agreed that this nodule was a benign ductal adenoma. Some audience members felt that this lesion may be at a stage of regeneration; however, this seemed unlikely because this nodule showed growth and expansion into the surrounding tissue and there was no inflammation or necrosis to indicate prior injury 19 .…”

<i>N</i>-Methyl-<i>N </i>-nitrosourea-induced Renal Tumors in Rats: Immunohistochemical Comparison to Human Wilms Tumors

“…N -Methyl- N -nitrosourea (MNU), a direct-acting alkylating agent that interacts with DNA, is toxic and carcinogenic to the immune, hematopoietic, reproductive, mammary, dentine, gastrointestinal, pancreatic, nervous and/or sensory systems 5 , 6 , 7 . Nitrosourea compounds including N -methyl- N -nitrosourea (MNU) also possess carcinogenic potency in the kidneys 8 , 9 , and MNU induces renal mesenchymal tumors (RMTs) and nephroblastomas in rats 10 , 11 , 12 .…”