Effect of etoposide, carmustine, vincristine, 5-fluorouracil, or methotrexate on radiobiologically oxic and hypoxic cells in a C3H mouse mammary carcinoma in situ.
The effect of etoposide (VP16), carmustine (BCNU), vincristine (VCR), methotrexate (MTX), and 5-fluorouracil (5-FU) on the oxic and hypoxic cells in a C3H mammary carcinoma in CDF1 mice was investigated using an in situ local-tumor-control (TCD50) assay. The surviving fraction (SF) was calculated from the size of the radiation dose needed to inactivate the surviving tumor cells in drug-treated tumors relative to untreated controls. Preferential drug cytotoxicity towards oxic and hypoxic cells was evaluated from the difference in the response to irradiation under ambient and clamped conditions, respectively. Three drugs caused a significant (P less than 0.05) reduction in the survival of hypoxic cells, the SFs being 0.31 (VP-16), 0.13 (BCNU) and 0.16 (VCR). VCR was also toxic towards oxic cells (SF, 0.17), whereas VP16 and BCNU had no significant effect on these cells (SF, 0.5 and 0.76, respectively). Two drugs produced significant killing of cells in the oxic compartment: 5-FU (SF, 0.10) and MTX (SF, 0.22); these two drugs had no effect on hypoxic cells (SF, 0.78 and 1.11, respectively).
Grau
C
C
Department of Experimental Clinical Oncology, Radiumstationen, Aarhus C., Denmark.
Overgaard
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000633:toxicity; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002330:Carmustine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects* / Q000528:radiation effects; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity
D000970:Antineoplastic Agents; D014750:Vincristine; D005047:Etoposide; D005472:Fluorouracil; D002330:Carmustine; D008727:Methotrexate