Toxicity of methylating agents in isolated hepatocytes

Reitman, F.; Shertzer, Howard G.; Berger, Marc L.

doi:10.1016/0006-2952(88)90318-8

Cited by 31 publications

(9 citation statements)

References 28 publications

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“…The liver is a potential target for such ROS-induced damage although endowed with a rich supply of antioxidants. An increase in lipid peroxidation was observed when hepatocytes were exposed to MNNG (Reitnan et al, 1988). Thus enhanced lipid peroxidation in the stomach and liver of MNNG treated animals in the present study may be attributed to excessive generation of ROS exacerbated by deficient antioxidant defenses.…”

Section: Discussionmentioning

confidence: 42%

Attenuation of N-methyl-N′-nitro-N-nitrosoguanidine induced genotoxicity and oxidative stress by tomato and garlic combination

et al. 2005

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Section: Discussionmentioning

confidence: 42%

Attenuation of N-methyl-N′-nitro-N-nitrosoguanidine induced genotoxicity and oxidative stress by tomato and garlic combination

et al. 2005

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“…Free radical-mediated oxidative stress has been implicated in the hepatotoxic effects of MNNG (Reitman et al, 1988). The reaction of MNNG with H 2 O 2 was demonstrated to produce toxic and highly diffusible hydroxyl radicals causing deleterious effects at sites far from the tumour (Mikuni et al, 1985;Dreher and Junod, 1996).…”

Section: Discussionmentioning

confidence: 99%

Garlic and neem leaf extracts enhance hepatic glutathione and glutathione dependent enzymes duringN-methyl-N?-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats

2000

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“…MMS rapidly methylates glutathione in vitro yielding S-methyl glutathione and providing an alternate methylation target [37]. MMS-mediated glutathione depletion has been documented previously in cultured hepatocytes, and, in these studies MMS toxicity was proposed to be a result of increased oxidative damage (lipid peroxidation) in addition to methylation of DNA [38, 39]. …”

Section: Resultsmentioning

confidence: 99%

Role of the oxidized form of XRCC1 in protection against extreme oxidative stress

Horton

Seddon

Zhao

et al. 2017

Free Radical Biology and Medicine

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The multi-domain protein XRCC1 is without catalytic activity, but can interact with a number of known repair proteins. The interaction between the N-terminal domain (NTD) of XRCC1 and DNA polymerase β (pol β) is critical for recruitment of pol β to sites of DNA damage and repair. Crystallographic and NMR approaches have identified oxidized and reduced forms of the XRCC1 NTD, and the corresponding forms of XRCC1 have been identified in cultured mouse fibroblast cells. Both forms of NTD interact with pol β, but the interaction is much stronger with the oxidized form. The potential for formation of the C12-C20 oxidized conformation can be removed by alanine substitution at C12 (C12A) cells expressing C12A XRCC1 (XRE8) with those expressing wild-type XRCC1 (XC5). Reduced C12A XRCC1 is detected at sites of micro-irradiation DNA damage, but provides slower recruitment of pol β. Expression of reduced XRCC1 does not affect sensitivity to MMS or H2O2. In contrast, further oxidative stress imposed by glutathione depletion results in increased sensitization of reduced XRCC1-expressing cells to H2O2 compared with wild-type XRCC1-expressing cells. There is no indication of enhanced H2O2-generated free radicals or DNA strand breaks in XRE8 cells. However, elevated cellular PAR is found following H2O2 exposure, suggesting BER deficiency of H2O2-induced damage in the C12A expressing cells.

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Toxicity of methylating agents in isolated hepatocytes

Cited by 31 publications

References 28 publications

Attenuation of N-methyl-N′-nitro-N-nitrosoguanidine induced genotoxicity and oxidative stress by tomato and garlic combination

Attenuation of N-methyl-N′-nitro-N-nitrosoguanidine induced genotoxicity and oxidative stress by tomato and garlic combination

Garlic and neem leaf extracts enhance hepatic glutathione and glutathione dependent enzymes duringN-methyl-N?-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats

Role of the oxidized form of XRCC1 in protection against extreme oxidative stress

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