Antitumour imidazotetrazines--XXIV. Growth suppression by DNA from cells treated with imidazotetrazinones.

Transfection of a murine colon adenocarcinoma cell line (MAC13) with DNA extracted from GM892 or Raji cells previously treated with either the methyl- (temozolomide) or ethyl-(CCRG82019) imidazotetrazinones caused a dose-related suppression of cell growth. The effect was proportional to the concentration of DNA transfected and the time of incubation of the donor cell lines with the drugs. It was not shown with X-irradiated DNA suggesting that the effect did not arise from non-specific damage to the DNA. Transfection of MAC13 cells with DNA extracted from GM892 cells was more effective in inhibiting growth than DNA from Raji cells, and temozolomide treated cellular DNA was a more potent growth inhibitor than that from CCRG 82019 treated cells. For both agents the growth inhibitory effect was most marked with DNA extracted 6 hr after drug addition and thereafter the effect decreased up to 24 hr after drug addition. This suggests that the growth inhibitory effect is due to a repairable lesion, and that the terminal mechanism of action of these agents involves targets after DNA.