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 Adriamycin or 4'-(9-acridinylamino)methanesulfon-m-anisidide uptake by thiourea. Experiments using nucleoid 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.
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics*; D004277:DNA, Single-Stranded / Q000235:genetics*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005609:Free Radicals; D007364:Intercalating Agents / Q000633:toxicity*; D007939:Leukemia L1210 / Q000503:physiopathology*; D051379:Mice; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000494:pharmacology*
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D005609:Free Radicals; D007364:Intercalating Agents; D013890:Thiourea; D004121:Dimethyl Sulfoxide