DNA single-strand breaks and cytotoxicity induced by sodium chromate(VI) in hydrogen peroxide-resistant cell lines. 1993

M Sugiyama, and K Tsuzuki, and N Haramaki
Department of Medical Biochemistry, Kurume University School of Medicine, Japan.

Hydrogen peroxide-resistant Chinese hamster ovary (CHOR) cells were developed by exposing parental (CHO(P)) cells to sequential increases in H2O2 concentration. Cytotoxicity as well as DNA single-strand breaks induced by Na2CrO4 were then compared in CHOR and CHO(P) cell lines. Using the colony-forming assay, it was found that the cytotoxicity caused by Na2CrO4 did not differ in the parent and resistant cells. However, alkaline elution studies showed that the production of DNA single-strand breaks in CHOR cells treated with Na2CrO4 was reduced by about 50% as compared with that in CHO(P) cells. Similarly, electron spin resonance (ESR) studies revealed that the level of chromium(V) in CHOR cells during treatment with Na2CrO4 was about 50% that in CHO(P) cells. CHOR cells were also found to be cross-resistant to the cytotoxicity and DNA breaks caused by other toxic metals such as CdCl2 and HgCl2. Catalase activity in resistant cells was 2-fold and the cellular content of glutathione was 3-fold that in parental cells. However, no obvious differences were seen in superoxide dismutase and glutathione reductase activity, although the contents of ascorbic acid or alpha-tocopherol were slightly decreased in CHOR cells, suggesting that the resistance in CHOR cells may be associated with the increase in both catalase activity and glutathione contents in cells. These results indicate that chromate-induced DNA breaks appear to be mediated by a different mechanism than that for the cytotoxicity of this metal, and also suggest that the formation of active oxygen species and/or chromium(V) during reduction of chromium(VI) inside cells might be associated with the induction of the DNA strand breaks caused by the metal.

UI MeSH Term Description Entries
D008627 Mercuric Chloride Mercury chloride (HgCl2). A highly toxic compound that volatizes slightly at ordinary temperature and appreciably at 100 degrees C. It is corrosive to mucous membranes and used as a topical antiseptic and disinfectant. Mercury Dichloride,Corrosive Sublimate,HgCl2,Mercuric Perchloride,Mercury Bichloride,Mercury Perchloride,Sublimate,Bichloride, Mercury,Chloride, Mercuric,Dichloride, Mercury,Perchloride, Mercuric,Perchloride, Mercury,Sublimate, Corrosive
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D002104 Cadmium An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.
D002374 Catalase An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA. Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D002712 Chlorides Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D002840 Chromates Salts of chromic acid containing the CrO(2-)4 radical. Chromate
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
D004277 DNA, Single-Stranded A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle. Single-Stranded DNA,DNA, Single Stranded,Single Stranded DNA
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D004578 Electron Spin Resonance Spectroscopy A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING. ENDOR,Electron Nuclear Double Resonance,Electron Paramagnetic Resonance,Paramagnetic Resonance,Electron Spin Resonance,Paramagnetic Resonance, Electron,Resonance, Electron Paramagnetic,Resonance, Electron Spin,Resonance, Paramagnetic

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