Effect of oxygen tension on the antitumor activity of mitomycin C assayed by human tumor clonogenic assay.

The effects of oxygen tensions on the antitumor activity of mitomycin-C (MMC) were surveyed using the human tumor clonogenic assay technique. Six human tumor xenografts (4 gastric cancers, and 2 colon cancers) were used in this study. Tumor cells were continuously exposed to MMC during the experimental period at various oxygen tensions, such as 2 per cent, which is considered to be hypoxic oxygen tension, 5 per cent which is considered as the physiological oxygen tension, and 20 per cent which is the conventional in vitro culture condition. The antitumor activities of MMC on the 6 human tumor xenografts increased when the oxygen tension was lowered from 20 per cent to 5 per cent. However, no further increases of the antitumor activities of MMC were observed by lowering the oxygen tension from 5 to 2 per cent. Additionally, the in vitro antitumor activities of MMC at various oxygen tensions were compared with the in vivo chemosensitivities evaluated in nude mice. In five of the 6 human tumor xenografts, in vitro chemosensitivities assayed at 2 or 5 per cent oxygen tension were concordant with in vivo chemosensitivities, although in vitro chemosensitivities assayed at 20 per cent were concordant with in vivo chemosensitivities in 3 of the 6 tested tumors.