Detection of in vivo genotoxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) by the alkaline single cell gel electrophoresis (Comet) assay in multiple mouse organs

Sasaki, Yu; Nishidate, Emi; Izumiyama, Fusako; Watanabe-Akanuma, Mie; Kinae, Naohide; Matsusaka, Naonori; Tsuda, Shuji

doi:10.1016/s1383-5718(97)00085-5

Cited by 50 publications

(18 citation statements)

References 22 publications

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“…However, we also detected a small percentage of cells exhibiting higher levels of DNA damage under basal conditions. Similar results have been obtained in previous studies in human lymphocytes and in various mouse organs (Arlett et al, 1993;Collins et al, 1995;Sasaki et al, 1997), and it is possible that this background level of DNA damage is caused by the nuclei isolation procedure. Obviously, we cannot rule out the possibility that the SSBs we detected are present in vivo under control conditions.…”

Section: Giovannelli Et Al 702supporting

confidence: 90%

Comet Assay as a Novel Approach for Studying DNA Damage in Focal Cerebral Ischemia: Differential Effects of NMDA Receptor Antagonists and Poly(ADP-Ribose) Polymerase Inhibitors

Giovannelli

Cozzi

Guarnieri

et al. 2002

J Cereb Blood Flow Metab

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Summary:The single-cell gel electrophoresis (comet assay) was used to evaluate the possibility of detecting single-strand breaks of brain DNA in the early phase of ischemia. Four hours after occlusion of the middle cerebral artery (MCAO) in rats, the percentage of DNA migrating into the comet tail (indicating the presence of breaks) increased from 11.4 ± 4.70 to 34.7 ± 9.2 (means ± SD) in the caudate and from 9.9 ± 4.3 to 42.8 ± 14.1 in the cortex. Interestingly, a subpopulation of cells exhibiting higher resistance to the ischemic insult was present in the caudate putamen, but not in the cortex. Administration of MK801, an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, (1 mg/kg subcutaneously, 10 minutes before MCAO), reduced the ischemia-induced DNA breaks and the infarct volume, suggesting that excessive stimulation of NMDA receptors contributes to the formation of both DNA damage and infarct volume. In contrast, DPQ, an inhibitor of poly(ADP-ribose) polymerase (PARP) (10 mg/kg intraperitoneally, 2 hours before and 1 hour after MCAO), reduced the infarct volume but not DNA damage, suggesting that the neuroprotective actions of PARP inhibitors occur at a later step of the processes leading to postischemic neuronal death. Key Words: Rat brain-Singlestrand breaks-Double-strand breaks-MK-801-DPQ-PARP.

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Section: Giovannelli Et Al 702supporting

confidence: 90%

Comet Assay as a Novel Approach for Studying DNA Damage in Focal Cerebral Ischemia: Differential Effects of NMDA Receptor Antagonists and Poly(ADP-Ribose) Polymerase Inhibitors

Giovannelli

Cozzi

Guarnieri

et al. 2002

J Cereb Blood Flow Metab

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“…On Day 7 of gestation, 4 successfully copulated females were assigned to each treatment and non-treated control group (4, 8, 12 and 24 hr). In our previous mouse Comet assays, we observed no significant differences in mean migration between vehicle control groups and corresponding untreated groups at any time for any organs [15][16][17][18]. The results enabled us to use untreated control animals as concurrent control animals.…”

Section: Animalsmentioning

confidence: 66%

Detection of in vivo DNA Damage Induced by Ethanol in Multiple Organs of Pregnant Mice Using the Alkaline Single Cell Gel Electrophoresis (Comet) Assay

Kido

Sato

Tsuda

2006

The Journal of Veterinary Medical Science

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ABSTRACT. Ethanol is principal ingredient of alcohol beverage, but considered as human carcinogen, and has neurotoxicity. Alcohol consumption during pregnancy often causes fetal alcohol syndrome. The DNA damage is one of the important factors in carcinogenicity or teratogenicity. To detect the DNA damage induced by ethanol, we used an in vivo alkaline single cell gel electrophoresis (Comet) assay in pregnant mice organs and embryos. Pregnant ICR mice on Day 7 of gestation were treated with 2, 4 or 8 g/kg ethanol, and maternal organs/tissues and embryos were subjected to the Comet assay at 4, 8, 12 and 24 hr after ethanol treatment. Four and 8 g/kg ethanol induced DNA damage in brain, lung and embryos at 4 or 8 hr after the treatment. Two g/kg ethanol did not cause any DNA damage, and 8 g/kg ethanol only increased the duration of DNA damage without distinct increase in the degree of the damage. No significant DNA damage was observed in the liver. To detect the effect of acetaldehyde, disulfiram, acetaldehyde dehydrogenase inhibitor, was administered before 4 g/kg ethanol treatment. No significant increase of DNA damage was observed in the disulfiram pre-treated group. These data indicate that ethanol induces DNA damage, which might be related to ethanol toxicity. Since pre-treatment of disulfiram did not increase DNA damage, DNA damage observed in this study might not be the effect of acetaldehyde. KEY WORDS: Comet assay, DNA damage, ethanol, pregnant mouse.

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“…Chlorine dose, TOC, and pH were also associated with increased mutagenicity. Seasonal differences were observed in the MX samples-higher concentrations were found in spring (10 ng/L; 95% CI, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] compared to fall ( Table 5). Communities that used filtration (-12 ng/L; 95% CI, -23 to -2) and chloramination (-17 ng/L; 95% CI, -27 to -6) had significantly lower MX levels compared to other methods of treatment.…”

Section: Resultsmentioning

confidence: 99%

“…MX has been shown to be one of the most potent bacterial mutagens tested (16). In addition to bacterial assays, MX is a direct-acting mutagen and genotoxin in vivo (17)(18)(19)(20)(21) and in mammalian cells in vitro (21)(22)(23)(24)(25)(26)(27). MX is a multisite carcinogen in male and female rats (6), with an estimated cancer potency 170 times greater than chloroform and 17 times greater than bromodichloromethane (28).…”

mentioning

confidence: 99%

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

Wright

Schwartz

Vartiainen

et al. 2002

Environ Health Perspect

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There is limited information on the prevalence of the potent mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in U.S. water supplies. We measured MX concentrations and mutagenic activity in tap water samples from 36 surface water systems throughout Massachusetts. We found MX levels much higher (up to 80 ng/L) than previously reported in the United States. We also evaluated the role of water treatment on mutagenic activity and disinfection by-product formation. After adjusting for other covariates, chloramination and filtration were the most important treatment options for reducing mutagenic activity and disinfection by-product formation. Multiple chlorine application (before and after filtration) was associated with increased mutagenicity. Chlorine dose, pH, and total organic carbon were also associated with mutagenicity, MX, and total trihalomethane (TTHM) concentration. Seasonal variation was evident for MX and mutagenic activity, with higher levels occurring in the spring compared to the fall. In contrast, TTHM concentrations were greater in the fall.

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Detection of in vivo genotoxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) by the alkaline single cell gel electrophoresis (Comet) assay in multiple mouse organs

Cited by 50 publications

References 22 publications

Comet Assay as a Novel Approach for Studying DNA Damage in Focal Cerebral Ischemia: Differential Effects of NMDA Receptor Antagonists and Poly(ADP-Ribose) Polymerase Inhibitors

Comet Assay as a Novel Approach for Studying DNA Damage in Focal Cerebral Ischemia: Differential Effects of NMDA Receptor Antagonists and Poly(ADP-Ribose) Polymerase Inhibitors

Detection of in vivo DNA Damage Induced by Ethanol in Multiple Organs of Pregnant Mice Using the Alkaline Single Cell Gel Electrophoresis (Comet) Assay

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

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