Ferritin Stimulation of Hydroxyl Radical Production by Rat Liver Nuclei

Kukielka, E.; Cederbaum, Arthur I.

doi:10.1006/abbi.1994.1010

Cited by 45 publications

(16 citation statements)

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“…This does not exclude the possibility of specific iron complexes with endogenous compounds that are redox‐active transition metals inside the cell, as suggested by Barbouti et al32 Several studies have indicated that NADH may react nonenzymatically with some xenobiotics and mediate their reduction 33, 34. The concentration of NAD(P)H in certain tissues has been estimated to be as high as 100–200 μM,35, 36 and the biologic importance of NADH and NADPH as nuclear reductants has been pointed out 37. Therefore, NADH may play an important role in the nonenzymatic activation of N ‐hydroxy derivatives in vivo.…”

Section: Discussionmentioning

confidence: 98%

Measuring sensitivity in gynecologic cytology: A review

Renshaw

2002

Cancer

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Section: Discussionmentioning

confidence: 98%

Measuring sensitivity in gynecologic cytology: A review

Renshaw

2002

Cancer

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“…[25][26][27] The biological importance of NADH and NADPH as nuclear reductants has been pointed out. 28) N-OH-AAB plus Cu(II) induced piperidine-labile sites preferentially at thymine and cytosine residues. Generally, site-specific and characteristic mutations have been found in human cancers as molecular mutational fingerprints associated with chemical carcinogens.…”

Section: Discussionmentioning

confidence: 99%

Oxidative DNA Damage Induced by an N‐Hydroxy Metabolite of Carcinogenic 4‐Dimethylaminoazobenzene

Ohnishi

Murata

Degawa

et al. 2001

Japanese Journal of Cancer Research

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Formation of adducts has been considered to be a major causal factor of DNA damage by carcinogenic aminoazo dyes. We investigated whether a metabolite of hepatocarcinogenic 4-dimethylaminoazobenzene (DAB) can cause oxidative DNA damage or not, using There is ample evidence for the carcinogenicity of 4-dimethylaminoazobenzene (DAB) in experimental animals. DAB induced lung tumors and hepatomas in mice and liver tumors in rats. In dogs it produced bladder tumors following oral administration. DAB has also been tested by s.c. injection in mice, and the results are suggestive of local and hepatic carcinogenicity.1) The International Agency for Research on Cancer (IARC) has assessed that DAB is possibly carcinogenic to humans (group 2B). 2)DAB is metabolized to N-methyl-4-aminoazobenzene (MAB) through N-demethylation. MAB is metabolized to 4-aminoazobenzene (AAB) through demethylation or to N-hydroxy-N-methyl-4-aminoazobenzene (N-OH-MAB) through N-hydroxylation, followed by further transformation to N-hydroxy-4-aminoazobenzene (N-OH-AAB). 3-5)N-Hydroxylation is believed to be a step leading aminoazo dyes to proximate carcinogenic or mutagenic metabolites. Watanabe and Hashimoto reported that N-OH-AAB elicited higher levels of unscheduled DNA synthesis (UDS) than AAB, suggesting higher DNA damaging activity of the N-hydroxy derivative than that of the corresponding mother aminoazo dye.6) It was also reported that N-OH-AAB dyes showed greater mutagenicity than the mother AAB dyes, without S-9 treatment.7) It is generally accepted that covalent binding of these metabolites with DNA is a major carcinogenic factor. 8) N-(Deoxyguanosin-8-yl)-4-aminoazobenzene was also obtained from mice or rats given an i.p. dose of AAB.4) It was regarded as an adduct formed by reaction of deoxyguanosine with a metabolite of AAB after N-hydroxylation and esterification. 4)On the other hand, N-OH-AAB and N-OH-MAB are reported to generate H 2 O 2 and O . 9) Administration of 3′-methyl-4-dimethylaminoazobenzene (3′-MeDAB) which is a stronger carcinogenic derivative of DAB, increased the levels of 8-hydroxyguanine and its repair activity in rodent liver DNA.10) These reports suggested that oxidative DNA damage plays a part in carcinogenesis by aminoazo dyes.To clarify the mechanism of carcinogenesis by DAB, we examined oxidative DNA damage induced by N-OH-AAB, using 32 P-5′-end-labeled DNA fragments obtained from the c-Ha-ras-1 protooncogene and the p53 tumor suppressor gene. In addition, we measured the content of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in calf thymus DNA by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD). It has been reported that 8-oxodG is a marker of oxidative DNA damage and that its formation can lead to DNA misreplication, resulting in mutation and cancer.

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“…[1-13 C] ethanol was used to confirm the formation of the 1-hydroxyethyl radical and to demonstrate that this was ethanol derived in rats given single-dose treatment [8]. In addition, superoxide radicals are capable of mobilizing iron from ferritin, thereby increasing the amount of catalytically active iron in hepatocytes [9]. Chronic ethanol consumption, damaging the mitochondrial respiratory chain, could result in increased electron leakage and superoxide production.…”

Section: Introductionmentioning

confidence: 99%