Phase-specific cytotoxicity in vivo of hydroxyurea on murine fibrosarcoma pulmonary nodules.
The cytotoxic effects in vivo of hydroxyurea (HU) on murine fibrosarcoma (FSa) cells grown as pulmonary tumours were determined. Tumour cells from 13-day-old nodules were made into suspension and separated on the basis of cell size by centrifugal elutriation. Flow microfluorometry (FMF) was used to determine the cell-cycle parameters and the relative synchrony of the separated populations, as well as the degree of contamination by normal diploid cells in each of the tumour-cell populations. HU cytotoxicity was tested by administering both a single 1 mg/g i.p. dose into mice that had been injected i.v. 20 min earlier with known numbers of synchronized viable FSa cells, and i.p. doses of 1 mg/g each into mice bearing 13-day-old pulmonary nodules. In the latter experiments, animals were killed 1 h after the last dose, and the tumour nodules were excised and made into a single-cell suspension and elutriated. Known numbers of cells from each fraction were injected into recipient mice to determine survival. In both sets of experiments, cell killing by HU correlated with the percentage of S-phase cells. The treatment of 13-day-old pulmonary nodules with 3 doses of HU also depleted the (G2+M) phase tumour cells and increased the heterogeneity between tumour subpopulations, as determined by FMF analysis.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005434:Flow Cytometry; D006918:Hydroxyurea / Q000627:therapeutic use*; D007399:Interphase / Q000187:drug effects*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008748:Methylcholanthrene; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology
D008748:Methylcholanthrene; D006918:Hydroxyurea