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Quantitation of the Cancer Process in C57BL/6J, B6C3F1 and C3H/HeJ Mice

ILS, Inc., Post Offi ce Box 13501, Research Triangle Park, North Carolina 27709

Ronny Fransson-Steen

AstraZeneca Safety Assessment, S-151 85 H. Sodertalje, Sweden

This study examines growth alterations in liver foci and tumor development as a basis for the different susceptibility in hepatocarcinogenes is found among different strains of mice. Male C57, B6C3F 1, and C3H mice treated with a single dose (1 mg/kg) of N,N-diethylnitrosamine (DEN) at 15 days of age and followed up to 12 months displayed a strain-dependent (C3H > B6C3F1 > C57) increase in incidence, number, volume fraction, and size of foci and macroscopic lesions (masses). DEN-treated mice exhibited a time-dependent increase in foci size but not in foci number. Phenobarbital (PB) treatment (500 ppm) in the drinking water starting 2 weeks after DEN-initiation did not affect the incidence or number of masses and foci. In all 3 strains, the bromodeoxyuridin e labeling index in foci correlated with foci growth, supporting the major role of cell proliferation in foci growth. Measurements of apoptosis by morphological criteria with H&E staining suggest that intrafocal apoptosis may be a late event preventing foci growth and possibly also promoting focal cell selection, whereas extrafocal apoptosis may facilitate clonal growth by removing adjacent normal cells. The onset of conversion of foci to masses also correlated with strain susceptibility to hepatocarcinogenesis .

Key Words: Liver • carcinogenesis • proliferation • hepatic foci • apoptosis • diethylnitrosamine • phenobarbital.

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Toxicologic Pathology, Vol. 30, No. 1, 97-105 (2002)
DOI: 10.1080/01926230252824770


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