Choline Deficiency, Partial Hepatectomy, and Liver Tumors in Rats and Mice

Abstract

Choline deficiency (CD) increases susceptability of the rat liver to a number of~epatocellular carcinogens with a wide diversity of structure and potency. While severe CD results in micronodular cirrhosis and enhanced tumor induction, even a mild deficiency, without cirrhosis is sufficient to result in the increased carcinogenic response. The effects of CD are in part mediated via modulation of microsomal and, possibly, cytosolic enzymes responsible for activation/deactivation of carcinogens.. The 86C3F1 hybrid mouse is remarkably sensitive to initiation/promotion of liver tumors by many substances or conditions. Choline deficiency or partial hepatectomy alone, or in concert, markedly enhances liver tumor induction in the absence of any known carcinogen. These data indicate that the liver of this strain of mouse is "initiated" at or shortly after birth and can be promoted by non-carcinogenic substances or conditions.

Diet: The Neglected Variable in Chemical Safety Evaluations

“…It was revealed that some of the methyl-deficient diets used in the rat studies were also contaminated with aflatoxin via the peanut meal used in the diet, clouding temporarily the issue of choline-deficiency hepatocellular cancer in rats (13). However, this was clarified by subsequent studies that showed that choline-deficient diets not only induced hepatocellular carcinomas in rats and mice (6,9,17,27) Steatosis, Mitogenesis, DNA, and Chromatin Analysis. Based on our observations using true-color image analysis of digital specimens (Fig.…”

Efficient tumorigenesis by mutation-induced failure to terminate microRNA-mediated adaptive hyperplasia

“…R-type AH, for a large number of tissues. For example, the close correspondence between wound repair and carcinogenesis in skin [240] was first shown nearly a century ago when tumors occurred predictably at sites of wounds made on tar-treated mouse skin [241], and rodent liver tumorigenesis has long been studied efficiently after liver damage induced by partial hepatectomy, hepatotoxic chemical exposure, or cirrhotogenic dietary nutrient (e.g., choline) deficiency [241][242][243][244][245]. Current methods to measure and interpret miRNA profiles [246] have revealed miRNA profiles that distinguish hyperplastic, benign neoplastic, and/or malignant cells in, e.g., adrenal glands [247,248], columnar mammary epithelium [249], thyroid follicles [250,251], endometrium [252], pancreas (beta cells) [253][254][255], prostate [256], smooth muscle [257], and keratinocytes [258,259].…”

Review of the carcinogenic activity of diethanolamine and evidence of choline deficiency as a plausible mode of action

“…Choline is an essential nutrient in all mammals, and dietary choline deficiency is known to promote spontaneous hepatocarcinogenesis in rodents (Newberne et al, 1982;DeCarmargo et al, 1985;Rogers et al, 1987). The principal source of choline in mammalian species is via their diet.…”