This Article Free Full Text (Free PDF) Free References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Diwan, B. A. Articles by Rice, J. M. Search for Related Content PubMed PubMed Citation Articles by Diwan, B. A. Articles by Rice, J. M. Social Bookmarking                         What's this?

Dissimilar Frequency of Hepatoblastomas and Hepatic Cystadenomas and Adenocarcinomas Arising in Hepatocellular Neoplasms of D2B6F1 Mice Initiated with N-Nitrosodiethylamine and Subsequently Given Aroclor-1254, Dichlorodiphenyltrichloroethane, or Phenobarbital

Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp

Jerrold M. Ward

Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201

Yasushi Kurata

Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201

Jerry M. Rice

Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201

Aroclor-1254 (Ar-1254) and dichlorodiphenyltrichloroethane (DDT) were compared to phenobarbital (PB) for their ability to promote hepatocellular proliferative lesions to hepatocellular adenomas and carcinomas and to hepatoblastomas in D2B6F1 male mice initiated with N-nitrosodiethylamine (NDEA). Hepatocellular neoplasms developed in all mice given NDEA and were more numerous in mice fed promoters. Multiplicities decreased in the order Ar-1254 > PB > DDT, indicating that Ar-1254 was more potent than either PB or DDT at the dosage levels used. PB was the most effective of the 3 agents in stimulating the evolution of hepatocellular neoplasms to hepatoblastoma. The incidence of hepatoblastomas in the NDEA.PB group was 72% but was only 27% in NDEA-initiated, DDT-promoted mice and 33% in low-dose and only 9% in high-dose Ar-1254-promoted mice. In contrast, lesions resembling benign and malignant cholangiocellular neoplasms were frequently found within hepatocellular tumors in Ar-1254-promoted mice but not in mice fed PB or DDT, either alone or after NDEA. Some cystic glandular structures in Ar-1254-promoted mice contained mucous cells, argentaffin cells, and Paneth cells and thus constituted intestinal metaplasia. Hepatoblastoma and intestinal metaplasia/cholangiocellular tumor morphology appear to constitute different patterns of genetic programming induced by certain promoters in expanding clones of initiated hepatocytes, on favorable genetic backgrounds such as that of D2B6F1 male mice.

Key Words: Differentiation • dedifferentiation • hyperplasia • intestinal metaplasia • promotion • progression

Toxicologic Pathology, Vol. 22, No. 4, 430-439 (1994)
DOI: 10.1177/019262339402200409


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				V. S. Turusov, M. Tor, R. C. Sills, G. A. Willson, R. A. Herbert, J. R. Hailey, J. K. Haseman, and G. A. Boorman Hepatoblastomas in Mice in the US National Toxicology Program (NTP) Studies Toxicol Pathol, August 1, 2002; 30(5): 580 - 591. [Abstract] [PDF]

				J. M. Ward, M.-A. Shibata, and D. E. Devor Emerging Issues in Mouse Liver Carcinogenesis Toxicol Pathol, January 1, 1996; 24(1): 129 - 137. [Abstract] [PDF]