Morphological maturation of tumor cells induced by ethylnitrosourea (ENU) in rat brains. II. On the tumors by administration of ENU in the mid-gestational stage.

In order to clarify the relationship between cellular characteristics of rat brain tumors and the administration time of chemical carcinogens, the incidence and morphology of microtumors in the offspring of five pregnant Sprague-Dawley rats injected with ethylnitrosourea (ENU) intraperitoneally on the 11th day of gestation (Group I) were compared with those of six pregnant rats injected with ENU on the 18th day of gestation (Group II). Twenty-four microtumors and 6 macrotumors were obtained in Group I and 58 microtumors and 5 macrotumors in Group II. Histologically, the macrotumors of Group I showed a poorly differentiated pattern which corresponded to primitive spongioblastomas in comparison with those of Group II which resembled human mature oligodendrogliomas, astrocytomas or mixed gliomas. The constituent cells of the microtumors of both groups were immature and were morphologically similar to each other. Immunohistochemically, the cells of microtumors of both groups were negative for Leu 7 and glial fibrillary acidic protein. Microtumors in Group I showed more infiltrative proliferation than those in Group II and had indistinct borders. The 3H-thymidine labeling index of the constituent cells of Group I was significantly higher than that of Group II (p less than 0.001). This study revealed that the constituent cells of microtumors of Group I, in spite of being morphologically similar with those of Group II, possess a greater growth potency than the latter. This difference in growth potency is responsible for the difference in the histological maturity of the macrotumors in each group. The difference in morphological maturation of enlarged gliomas induced by ENU appears to depend on the imperceptible difference of the target cell maturation at the initiation of oncogenesis.