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Strain Specific Sensitivity to Diethylnitrosamine-induced Carcinogenesis Is Maintained in Hepatocytes of C3H/HeNC57BL/6N Chimeric Mice¹

Department of Pathology, Cancer Institute, Toshima-ku, Tokyo 170 [G-H. L., K. N., H. K., T. K.], and Laboratory of Cell Biology, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Ibaraki 305 [M. K., A. Y., T. S.], Japan

The C3H/HeN (C3H) and C57BL/6N (C57) mouse strains are known, respectively, for their high and low susceptibility to both spontaneous and chemically induced hepatocarcinogenesis. The present study was aimed at elucidating whether this difference is dependent on intrinsic features of the target hepatocytes or the in vivo milieu and associated growth promoting factors to which the cells are exposed. C3HC57 chimeric mice were produced and given injections of diethylnitrosamine (20 µg/g body weight) at the age of 15 days. The animals were sacrificed 6 or 9 months thereafter, and the numbers and sizes of altered cell lesions were scored. The clonal growth of both cell types was immunohistochemically confirmed using anti C3H-specific antigen antibodies. Quantitative assessment revealed C3H lesions in the chimera livers to be far larger (5:1) than those of C57 derivation and associated with more frequent malignant progression as was evident histologically. Furthermore, foamy change and hyalin body formation, which have been described as characteristics of C3H and C57BL hepatic tumors, respectively, were also featured as differentiative characteristics in lesions of both cell types in chimera mice. Thus, the results clearly demonstrated that the principal mechanism(s) underlying strain difference in diethylnitrosamine-initiated hepatocarcinogenesis exists in the target cells and is not milieu-dependent.

¹ Supported by Grants-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare of Japan, and by Grants from the Princess Takamatsu Cancer Research Fund.

² To whom requests for reprints should be addressed.

Received 12/10/90. Accepted 4/ 1/91.

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