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Liver adenomas and carcinomas: correlations and relationship to body weight in long-term rodent cancer bioassays

Harvard Center for Risk Analysis, Harvard School of Public Health, 718 Huntington Avenue, Boston, Massachusetts 02115,, ggray{at}hsph.harvard.edu

Igor Linkov

Menzie-Cura Associates, 1 Courthouse Lane, Suite 2, Chelmsford, Massachusetts 01824

Michael Polkanov

Department of Physics, Harvard University, Jefferson Laboratories, Cambridge, Massachusetts 02138

Richard Wilson

Department of Physics, Harvard University, Jefferson Laboratories, Cambridge, Massachusetts 02138, wilson{at}heplaxp3.harvard.edu

The most common cancers induced in laboratory rodents are liver cancers—both adenomas and carcinomas. There has been a long argument about the relative merits of combining them or considering them separately in the interpretation of long-term bioassays for chemical carcinogenesis. In this paper, we examine various aspects of the liver adenomas and liver carcinomas as seen in the Carcinogenesis Bioassay Data System (CBDS) and Toxicology Database Management System (TDMS) databases of the National Toxicology Program (NTP). It appears that the data themselves demonstrate interesting differences between the behavior of these tumors that probably have biological origin. Specifically, we find a strong negative correlation between the appearance of adenomas and carcinomas in the same animal in both control and chemically treated groups. This relationship does not seem to result from differential survival but may be influenced by the animal's body weight. Our analysis is generally consistent with either a progression of tumors from adenoma to carcinoma or a pathologist bias (that when a carcinoma is discovered, other tumors are ignored) as possible explanations for the negative correlation. However there are some differences between male and female mice that are puzzling. While we recognize the scientific and policy reasons for combination of adenomas and carcinomas for calculations of carcinogenic potency and risk we hope that toxicologists and pathologists will be encouraged to preserve the pathological distinctiveness of the two tumor types when analyzing rodent bioassays.

Key Words: adenomas • carcinomas • liver cancer • rodent bioassays

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