Human tumor strains defective in the repair of alkylated DNA fail to regenerate rapidly-sedimenting nucleoids after N-methyl-N' -nitro-N-nitrosoguanidine treatment

Upon treatment with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG),human cell strains characterized as either proficient or defectiveboth in repair of alkyla-tion-damaged DNA and in supportingthe growth of MNNG-treated adenovirus (Mer⁺ and Mer^– pheno-types(1,2), all underwent a rapid relaxation of nucleokl DNA, asjudged by sedimentation in 15–30% neutral sucrose gradients.DNA in the repair-proficient Mer⁺ strains (normal fibroblastand tumor) was restored to the rapidly-sedimenting (control)form within 2–4 h after the removal of MNNG. In contrast,nucleoid DNA of the repair-deficient Mer^– tumor strainsremained slowly-sedimenting even after 48 h of incubation. Thedelayed recovery of Mer^– nucleoid DNA was specific forMNNG damage, since after u.v. irradiation, to which Mer⁺ andMer^– strains are equally resistant (2), all cell linestested underwent DNA relaxation within the first hour afterirradiation (3 J/m²) and regenerated rapidly-sedimenting nucleoidswithin 4–6 h of repair incubation.