Effects of arsenic on DNA damage and repair in human fetal lung fibroblasts. 1994

J T Dong, and X M Luo
Cancer Institute, Chinese Academy of Medical Sciences, Beijing.

Previous studies suggest that arsenic may be both mutagenic and co-mutagenic. In this report, we examined the effects of sodium arsenite (As) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on unscheduled DNA synthesis (UDS) in human fetal lung fibroblasts (2BS cells) by 3H/14C double-labeling and liquid-scintillation counting techniques. Arsenic at concentrations of 1, 5 and 10 microM increased UDS value, indicating that arsenic directly damaged DNA and did not inhibit DNA repair. In addition, UDS induced by 34 microM MNNG in combination with arsenic was significantly increased by 3 microM As and not affected by 0.1, 0.5, 1.0 and 5 microM As, also indicating that arsenic did not inhibit the excision and polymerization steps of DNA repair. Based on the results and a previous study that 3 microM As is more efficient than 1 and 5 microM As in the induction of DNA-protein crosslinks, we proposed that arsenic may enhance the mutagenicity of other compounds by inducing DNA-protein crosslinks rather than inhibiting DNA repair.

UI MeSH Term Description Entries
D008769 Methylnitronitrosoguanidine A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties. Methylnitrosonitroguanidine,Nitrosomethylnitroguanidine,Nitrosonitromethylguanidine,MNNG,N-Methyl-N'-nitro-N-nitrosoguanidine,N Methyl N' nitro N nitrosoguanidine
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001151 Arsenic A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed) Arsenic-75,Arsenic 75

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