Effects of Dimethyl Sulfoxide and Thiourea upon Intercalator-induced DNA Single-Strand Breaks in Mouse Leukemia (L1210) Cells

The free radical scavengers, dimethyl sulfoxide (Me₂SO) and thiourea, were used to assess the role of free radicals in the production of intercalator-induced DNA breaks and cytotoxicity in mouse leukemia L1210 cells. Both agents decreased X-ray break production, and this decrease was comparable in magnitude to the degree of inhibition of X-ray-induced cell killing. By contrast, Me₂SO increased the DNA breaks produced by the intercalators, Adriamycin 5-iminodaunorubicin, and 4’-(9-acridinylamino)methanesulfon-m-anisidide. This was not due to an enhancement of Adriamycin or 4’-(9-acridinylamino)methanesulfon-m-anisidide uptake by Me₂SO. Strand break production by intercalators was decreased by thiourea. This was not due to an inactivation of the intercalators or to a decrease of Adriatnycin or 4’-(9-acridinylamino)methanesulfon-m-anisidide uptake by thiourea. Experiments using nudeoid sedimentation to assess the DNA linking number and domain size from cells treated with Me₂SO and thiourea indicated that these chemicals alter chromatin structure in a fashion which may account for effects on intercalator-induced DNA scission. The alterations in intercalator-induced DNA scission were not accompanied by corresponding alterations in cytotoxicity, thus dissociating intercalator-induced strand break production from lethality and the mechanism of X-ray break production.