Different cytotoxic effects of methyl- and ethylnitrosourea on developing rat tissues and the influence of cycloheximide on cell death.

Abstract

8 days old rats were exposed to 100 mg/kg b. w. of either Methylnitrosourea (MNU) or Ethylnitrosourea (ENU). In the extraneural tissues mitotic inhibition lasts longer after MNU than after ENU. In the case of ENU, the number of mitotic cells rapidly increases once they reappear, whereas in the MNU-treated material reappearing mitotic figures are present in small numbers only at all intervals studied. Lethally damaged cells disappear slowly, but at the same rate for both MNU and ENU. The neural tissues show a much longer duration of mitotic inhibition. But as in the extraneural tissues after their reappearance in ENU-treated animals mitotic figures rapidly increase in number, whereas after MNU only a very limited number of cells in mitosis is found at all intervals. Lethally damaged cells in the neural tissues disappear much later than in the extraneural ones, but again at the same rate for both MNU and ENU. Among the mitotic figures in all tissues examined abnormal ones are frequently noticed. Delay of cellular death was observed in all tissues examined when — after exposure to MNU or ENU — protein synthesis was blocked by cycloheximide, indicating that cell death is an active process depending on de novo synthesis of protein(s). In comparison with similar results for well-known alkylantia in the literature, our findings add further evidence that the cytotoxic action of both MNU and ENU is caused by alkylation of cellular macromolecules. The marked differences for mitotic inhibition between MNU and ENU may be significant with respect to the well-known difference in LD-50 of these compounds.