Mutagenesis by the autoxidation of iron with isolated DNA.

Loeb, Lawrence A.; James, Elizabeth A.; Waltersdorph, A M; Klebanoff, Seymour J.

doi:10.1073/pnas.85.11.3918

Cited by 137 publications

(56 citation statements)

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“…Experimental evidence of the mutagenicity and mitogenicity of iron in tissue supports this conclusion. [23][24][25] The precise way or ways in which increased tissue iron may contribute directly to hepatocarcinogenesis are, however, yet to be determined. One possible mechanism is that free cellular iron may induce mutations by generating reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

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Dietary iron overload as a risk factor for hepatocellular carcinoma in black africans

et al. 1998

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Although the iron-loading disease, hereditary hemochromatosis, has a strong causal association with hepatocellular carcinoma (HCC), the carcinogenic potential of dietary iron overload in Black Africans is not known. We investigated this potential by evaluating iron status, alcohol consumption, markers for hepatitis B (HBV) and C virus (HCV) infections, and exposure to dietary aflatoxin B 1 in 24 rural patients with this tumor, 48 race-, sex-, and age-matched hospital-based controls, and 75 related or unrelated close family members of the cancer patients. Iron overload was defined as a raised serum ferritin concentration in combination with a transferrin saturation H60%, and was confirmed histologically when possible. Among 24 patients and 48 hospital controls, the risk of developing HCC in the iron-loaded subjects was 10.6 (95% confidence limits of 1.

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Section: Discussionmentioning

confidence: 99%

“…One possible mechanism is that free cellular iron may induce mutations by generating reactive oxygen species. [23][24][25] A number of DNA changes are produced by reactive oxygen species. These include base changes, some of which have been shown to be mutagenic, 26 breakage of DNA strands, 27 and effects on apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Dietary iron overload as a risk factor for hepatocellular carcinoma in black africans

et al. 1998

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“…Thus it has been shown that singlet oxygen (O 2 ) induces a spectrum of mutations in bacteriophage quite distinct from the spectrum of mutations observed for spontaneous mutants (16) and that iron-generated oxygen species (presumably H 2 O 2 and -OH) generate specific types of mutations at a single bacteriophage amber site (17).…”

Section: Introductionmentioning

confidence: 99%

Mutagenesis by hydrogen peroxide treatment of mammalian cells: a molecular analysis

Moraes¹,

Keyse²,

Tyrrell³

1990

Carcinogenesis

113

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Hydrogen peroxide is an oxidizing agent which can be generated intracellularly either during normal metabolism or by treatment with external agents including solar UV radiation. Simian cells (CV-1) transfected with the SV40-based shuttle vector plasmid pZ189 have been treated with H 2 O 2 and then incubated to allow repair and replication of the plasmid. The frequency of mutations at the supF locus of the recovered plasmid increases by a factor of up to four over the spontaneous value. The nucleotide changes associated with 100 spontaneous and 100 H 2 O 2 -induced mutants have been determined directly by sequencing a 150 bp fragment that includes the entire supF tRNA coding region. Deletions were observed in -45% of both the spontaneous and induced mutants, whereas single or multiple base changes arose in 68 and 57% of the induced and spontaneous mutants respectively. The spectrum of induced mutations is characterized by (i) the occurrence of deletions associated with base changes (16% of all mutants analysed) and (ii) small deletions of 3 bp and less (51% of all deletion mutants sequenced). Sixty-five per cent (15 out of 23) of all small deletions (spontaneous and induced) are associated with runs of between two and five identical bases and eight of them arise at a mutational 'hotspot' region of five cytosines between bp 172 and 176. The majority (19 out of 30) of completely sequenced deletions observed in the spontaneous spectrum contain either (i) small (2-10 bp) direct repeat sequences that lie immediately outside one deletion terminus and immediately inside the second deletion terminus or (ii) small (2-3 bp) inverted repeat sequences lying immediately inside the two deletion termini. Most deletions that we have observed are therefore likely to arise as a consequence of specific aspects of DNA structure. IntroductionOxygen radicals appear to be involved in both the ageing process and in the initiation and progression of many human diseases, including cancer. A knowledge of the nature of mutations arising in DNA as a result of oxygen radical attack should provide important clues to understanding the molecular events that underlie these pathological changes. The characterization of the genotoxic action of the oxidizing agent, hydrogen peroxide, is particularly relevant in this respect for several reasons. In addition

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“…With progressively increasing Fe deposition, the capacity to maintain Fe in storage forms is exceeded resulting in a transient increase in the hepatic LIP [50]. Moreover, Fe-catalyzed generation of ROS has been implicated in the pathogenesis of many disorders including atherosclerosis [51,52], cancer [53], ischaemia reperfusion injury [54,55] besides in Fe overload [56], such as haemochromatosis [57].…”

Section: Fe Overload In Mammalsmentioning

confidence: 99%