The effects of three bioreductive drugs (mitomycin C, RSU-1069 and SR4233) on cell lines selected for their sensitivity to mitomycin C or ionising radiation.
We have investigated the cross-sensitivity of a number of cell lines to three different classes of bioreductive drugs under both aerobic and hypoxic conditions. The cell lines used were selected for their sensitivity to DNA-damaging agents and fall into two groups. One group, MMC cells derived from CHO-K1 cells (Robson et al., 1985), show a range of sensitivities to mitomycin C in air. The second group, irs cells were cloned from V79 Chinese hamster fibroblasts (Jones et al., 1987) and exhibit sensitivity to ionising radiation. The sensitivity of both groups of cells to mitomycin C (MMC), RSU-1069 and SR4233 was assessed under aerobic and hypoxic conditions. No difference in aerobic or hypoxic toxicity of MMC was observed for CHO-K1 or MMC sensitive cell lines (MMC-2 and MMC-3). However, the MMC-resistant cell line (MMCr) was 10 times more sensitive under hypoxic than aerobic conditions. This suggests that MMCr cells lack or are deficient in the enzymes responsible for activating MMC under aerobic conditions compared to other MMC cells. In contrast, differential toxicities of between 3 and 30 have been observed for all CHO cells treated with RSU-1069 and SR4233. Treatment of V79 and irs cells with RSU-1069 and SR4233 also resulted in selective toxicity towards hypoxic cells. Differential toxicities between 50 and 100 were observed for V79 cells. For both RSU-1069 and SR4233, the hypoxic toxicities were similar in V79 and irs cells but in air, the radiation sensitive cells were up to 10 times more sensitive than wild type cells.
Keohane
A
A
MRC Radiobiology Unit, Chilton, Didcot, Oxon, UK.
Godden
J
J
Stratford
I J
IJ
Adams
G E
GE
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D000077704:Tirapazamine; D014227:Triazines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008937:Mitomycins; D011838:Radiation-Sensitizing Agents; D014227:Triazines; D000077704:Tirapazamine; D016685:Mitomycin; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole