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Hepatoblastomas in Mice in the US National Toxicology Program (NTP) Studies

NN Blokhin Cancer Research Centre, 24 Kashirskoye Shosse, 115446 Moscow, Russian Federation

Mikinori Tor

Drug Safety Evaluation, Developmental Research Labs., Shionogi and Co., Ltd, 3-1-1 Futaba, Toyonaka, Osaka 561-0825, Japan

Robert C. Sills

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709

Gabrielle A. Willson

Experimental Pathology Laboratories, PO Box 12766, Research Triangle Park, North Carolina 27709, USA

Ronald A. Herbert

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709

James R. Hailey

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709

Joseph K. Haseman

Environmental Diseases and Medicine Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709

Gary A. Boorman

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709, boorman{at}niehs.nih.gov

Over the last 8 years, a 5-fold increase in the incidence of mice with spontaneous hepatoblastomas and a moderate increase in the incidence of chemically induced hepatoblastomas in B6C3F1 mice occurred in 2-year NTP studies compared to the previous 7 years. There was a positive association between an increased incidence of mice with hepatoblastoma and an increased incidence of mice with hepatocellular tumors in the treated mice. The rate of pulmonary metastases for hepatoblastoma was similar to that of pulmonary metastasis for hepatocellular carcinomas. Although a variety of chemicals caused an increased incidence of mice with hepatoblastoma, there was no apparent association between a specificchemical structure or a biological class of compounds and their capacity to induce hepatoblastomas. Hepatoblastomas frequently arose within hepatocellular carcinomas or adenoma s and were induced by the same compound s that induced hepatocellular neoplasms. Therefore, it seems reasonable to combine the incidence of mice with hepatoblastomas and the incidence of mice with hepatocellular carcinomas in hazard identification studies.

Key Words: Hepatocellular tumors • adenoma • rodent studies • cancer • B6C3F1 mice • cancer rates • bioassays • 2-year studies • embryonal tumors.

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Toxicologic Pathology, Vol. 30, No. 5, 580-591 (2002)
DOI: 10.1080/01926230290105802


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