We investigated to clarify the mechanism of action of AK-2123. V79 cells were used, and the effect of the substance was estimated with different end-points viz. induction of DNA breaks, micronuclei and clonogenic survival after hypoxic irradiation with different X-ray doses. After treatment with 0.1 mmol dm(-3) of the substance, sensitization by a factor of 1.8, 1.1 and 1.4 respectively, was calculated. By determining the enhancement ratio after treatment with the drug at 7-8 different concentrations varying between 0.001 and 50 mmol dm(-3), the concentration of the substance for half of the maximum sensitization (K-value) was estimated to be 40 mu mol dm(-3) (DNA breaks), 1200 mu mol dm(-3) (micronuclei) and 2000 mu mol dm(-3) (survival); the maximum sensitizer enhancement ratio was 2.4 (DNA breaks), 2.3 (micronuclei) and 2.4 (survival). No cytotoxic effects were found when the cells were treated with the drug in different concentrations for 30 minutes. However, after longer periods the compound was found to be cytotoxic both under aerobic and hypoxic conditions, in a concentration and time dependent manner. A post-irradiation enhancement of the sensitivity was noted when the drug was left in the medium for 24 hours after hypoxic as well as aerobic radiation exposure.

Related Articles