Immediate and Delayed Effects of Nitrogen Mustard on Cell Replication in an Autogenous Rat Sarcoma

Summary

Rats with 3-methylcholanthrene-induced autogenous sarcomas received 0.1 mg/kg nitrogen mustard (HN₂) daily for up to 7 days, and cell proliferation was studied by continuous labeling with tritiated thymidine. During HN₂ administration tumor growth stopped, the mitotic indices fell, and interphase and mitotic labeling was markedly reduced. The unlabeled mitoses were derived from G₂₀ cells. When present, labeling was light in tumor cells as well as in coexistent ileal crypt cells and spleen lymphocytes. When HN₂ was discontinued, tumor growth resumed at the pretreatment rate. The labeling of mitoses increased as did the levels of the mitotic indices. However, the recovery of the interphase labeling indices to pretreatment levels lagged behind these latter two parameters. Thus the pretreatment growth rate was associated with a reduced proliferating cohort of cells.