title: Human tumor cell strains defective in the repair of alkylation damage.
abstract: We have previously identified four human astrocytoma cell strains as defective in the repair of N-methyl-N' -nitro-N-nitrosoguanidine (MNNG) damaged adenovirus 5. We now show that two of these strains (the only two tested), in comparison to other tumor strains or normal human skin fibroblasts, are very sensitive to MNNG-produced killing as measured by colony forming ability, but are normally sensitive to ultraviolet light. Further, such repair deficient cells may be cultured from tumors of the colon, lung, skin, and neck. The phenotype of deficient repair of MNNG-treated adenovirus 5 has now been found in a subgroup of 9 of the 39 human tumor strains tested. We propose to call this phenotype the Mer(-) phenotype. None of the 22 strains of normal human skin fibroblasts tested showed deficient repair of MNNG damage. MNNG treatment (80 microM) causes a decrease in semi-conservative DNA synthesis from which Mer(-) tumor cells do not recover, but from which cells capable of normal repair of MNNG damage (Mer(+)) do. Somewhat paradoxically, Mer(-) cells show more MNNG-stimulated DNA synthesis ('repair synthesis') than do Mer(+) cells. Besides being deficient in the repair of MNNG-damaged adenoviruses Mer(-) cells also have difficulty in repairing viruses damaged either by other N-alkyl-N'-nitro-N-nitrosoguanidines, or by N-methyl- or N-ethyl-N-nitrosoureas.
authors.affiliation: Nucleic Acids Section, Laboratory of Molecular Carcinogenesis, CIP, DCCP, NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20034, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Day
authors.forename: C H
authors.initials: CH
authors.lastname: Ziolkowski
authors.forename: D A
authors.initials: DA
authors.lastname: Scudiero
authors.forename: S A
authors.initials: SA
authors.lastname: Meyer
authors.forename: M R
authors.initials: MR
authors.lastname: Mattern
mesh_terms: D000260:Adenoviruses, Human / Q000187:drug effects / Q000254:growth & development*; D000478:Alkylation; D000818:Animals; D001859:Bone Neoplasms / Q000503:physiopathology*; D002470:Cell Survival; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000009:adverse effects*; D051379:Mice; D012516:Osteosarcoma / Q000503:physiopathology*; D010641:Phenotype; D014466:Ultraviolet Rays / Q000009:adverse effects; D010948:Viral Plaque Assay
chemical_list: D004273:DNA, Neoplasm; D008769:Methylnitronitrosoguanidine