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Toxicologic Pathology
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Journal Article

Comparative Changes in the Liver of Female Fischer-344 Rats after Short-Term Feeding of a Semipurified or a Semisynthetic L-Amino Acid-Defined Choline-Deficient Diet

Dai Nakae

Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Nara 634, Japan

Yasushi Mizumoto

Department of Oncological Pathology, Cancer CenterNara Medical University, Kashihara, Nara 634, Japan

Nobuaki Andoh

Department of Oncological Pathology, Cancer CenterNara Medical University, Kashihara, Nara 634, Japan

Kazutoshi Tamura

Department of Oncological Pathology, Cancer Center, Cancer CenterNara Medical University, Kashihara, Nara 634, Japan

Kohsuke Horiguchi

Department of Oncological Pathology, Cancer Center, Cancer CenterNara Medical University, Kashihara, Nara 634, Japan

Takehiro Endoh

Department of Oncological Pathology, Cancer Center, Cancer CenterNara Medical University, Kashihara, Nara 634, Japan

Eisaku Kobayashi

Department of Oncological Pathology, Cancer Center, Cancer CenterNara Medical University, Kashihara, Nara 634, Japan

Toshifumi Tsujiuchi

Department of Oncological Pathology, Cancer Center, Cancer CenterNara Medical University, Kashihara, Nara 634, Japan

Ayumi Denda

Department of Oncological Pathology, Cancer Center, Cancer CenterNara Medical University, Kashihara, Nara 634, Japan

Benito Lombardi

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA

Yoichi Konishi

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA

Groups of female Fischer-344 rats were fed a semipurified choline-deficient (CD) diet, or a semisynthetic L-amino acid-defined choline-deficient (CDAA) diet, for up to 12 wk and effects of the 2 diets on the liver were compared. Steatosis was diffuse and more severe throughout in rats fed the CDAA diet than in rats fed the CD diet. Greater elevations in serum aspartate and alanine aminotransferase activities were also present in the former rats, along with higher 2-bromodeoxyuridine labeling indices in the liver. Discrete amounts of 8-hydroxyguanine were detected in liver DNA, but were not significantly different in rats fed the 2 diets, or from those present in a group of control rats killed at 0 time. Glutathione S- transferase placental form-positive focal lesions were not observed in any of the rats. The results show that the CDAA diet causes more severe degrees of steatosis and liver cell death and proliferation than the CD diet, raising the possibility that it may, in contrast to the CD diet, result in the eventual induction of hepatocellular carcinomas in female Fischer-344 rats.

Key Words: Dietary choline deficiency • hepatocarcinogenesis • histopathology • liver steatosis • liver cell necrosis • regenerative cell proliferation • glutathione S-transferase placental form-positive hepatocyte focal lesion • 8-hydroxyguanine

Toxicologic Pathology, Vol. 23, No. 5, 583-590 (1995)
DOI: 10.1177/019262339502300504
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