The etiology of breast cancer characteristic alterations in hydroxyl radical-induced dna base lesions during oncogenesis with potential for evaluating incidence risk

Malins, Donald C.; Gunselman, Sandra J.; Holmes, Eric H.; Polissar, Nayak L.

doi:10.1002/1097-0142(19930515)71:10<3036::aid-cncr2820711025>3.0.co;2-p

Cited by 195 publications

(111 citation statements)

References 25 publications

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“…GC-MS analysis of the samples was conducted by using a Hewlett-Packard model 6890 gas chromatograph with a Hewlett-Packard model 5973 mass spectrometer. The purine base lesions quantified were 8-OH-Gua, 8-hydroxyadenine (8-OH-Ade), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapyguanine; FapyGua), and 4,6-diamino-5-formamidopyrimidine (Fapyadenine) (21). The concentrations were reported as base lesions per 10 5 parent bases (4).…”

Section: Gc-msmentioning

confidence: 99%

Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors

Malins

Johnson

Barker

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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113

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Using statistical analyses of Fourier transform-IR spectra, we show that DNA of the histologically normal prostates of men 16 -80 years old undergoes structural changes in the bases and backbone with increasing age. Of the older men (ages 55-80), 42% exhibited a DNA phenotype mimicking that of primary prostate tumors from a comparable age group. This cancer-like phenotype, which was not found in the younger men (ages 16 -36), appears to arise from progressive age-related damage to DNA. The mean concentrations of 8-hydroxypurine lesions (e.g., 8-hydroxyguanine) were substantially higher for the older men than for the younger men. This finding suggests that the hydroxyl radical contributed to the structural changes that characterize the cancer-like phenotype. Strikingly, we were additionally able to discriminate between the DNA of primary prostate tumors and the DNA of primary prostate tumors from which distant metastases had been identified. Moreover, logistic regression analysis was able to predict the probability that a tumor had metastasized with Ϸ90% sensitivity and specificity. Collectively, these findings are particularly promising for identifying men at risk for developing prostate cancer, as well as for the early determination of whether a primary tumor has progressed to the metastatic state. This is highly important because the prognosis of histologically similar prostate carcinomas varies, thus creating a need to predict which cancers are most likely metastatic.I n the United States, prostate cancer is the most prevalent of all cancers and the second-leading cause of cancer mortality in men (1). The incidence rates for this disease rise markedly as a function of increasing age (1-3). Notably, 70% of all newly diagnosed prostate cancers occur in men over age 65 (2). The greatest threat from prostate cancer lies in its potential to metastasize (3). Clinical diagnosis of metastatic prostate cancer presently depends on histological identification of distant metastases. Yet, by the time the tumor has metastasized, the success of intervention is severely limited. Clearly, there is a need to identify early subcellular changes in the prostate, such as in DNA, associated with aging, primary tumor development, and the progression to metastasis.We have reported (4) that the ratio of mutagenic 8-hydroxy to putatively nonmutagenic ring-opened purine lesions in prostate DNA increased Ϸ3-fold in men between the ages of 16 and 83. In addition, a related study (5) showed a substantial accumulation of 8-hydroxyguanine (8-OH-Gua) in the liver, kidney, and intestine as rats aged. It was later reported (6) that levels of this base lesion increased 186% in the livers of rats between 5 and 30 months. Several factors have been suggested to explain agerelated increases in DNA base lesion concentrations in various tissues, among them reduced enzyme repair (7-10), a slow loss of DNA nuclease activity (5), and an increase in base oxidation (11). These findings focus attention on the importance of age-related free radical damage to...

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Section: Gc-msmentioning

confidence: 99%

Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors

Malins

Johnson

Barker

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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113

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“…Cancer and the Diet (53)(54)(55)(56)(57). The ways in which antioxidants might interfere with tumorigenesis are outlined in Figure 1.…”

Section: Other Mechanismsmentioning

confidence: 99%

Cigarette Smoke Radicals and the Role of Free Radicals in Chemical Carcinogenicity

Pryor¹

1997

Environmental Health Perspectives

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This article consists of two parts: a brief overview of the ways in which free radicals can be involved in chemical carcinogenesis, and a review of cigarette smoke chemistry. Carcinogenesis is generally agreed to involve at least three stages: initiation, promotion, and progression. It is suggested that radicals sometimes are involved in the initiation step, either in the oxidative activation of a procarcinogen (such as benzo[alpyrene) to its carcinogenic form or in the binding of the carcinogenic species to DNA, or both. The fraction of initiation events that involve radicals, as opposed to two-electron steps, is not known, but radicals probably are involved in a substantial number, although probably not a majority, of cancer initation reactions. Promotion always involves radicals, at least to some extent. Progression probably does not normally involve radicals. The second part of this article reviews the molecular mechanisms involved in cigarette-induced tumors, particularly by aqueous cigarette tar (ACT) extracts and by a model of these solutions, aged solutions of catechol. ACT solutions as well as aged solutions of catechol contain a quinone-hydroquinone-semiquinone system that can reduce oxygen to produce superoxide and hence hydrogen peroxide and the hydroxyl radical. Both the cigarette tar radical and the catecholderived radical can penetrate viable cells, bind to DNA, and cause nicks.Environ Health Perspect 1 05(Suppl 4): 875-882 (1997)

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“…Understanding the pathways of DNA damage and repair may be helpful in modulating drug and radiation resistance. There is evidence of high oxidative damage in breast cancer (Malins et al, 1993;Thorgeirsson et al, 1993) and therefore assessment of this major rate-limiting step in repair of these pathways was undertaken. (Needham et al, 1988;Horak et al, 1992).…”

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confidence: 99%

Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis

Kakolyris

Kaklamanis²,

Engels³

et al. 1998

Br J Cancer

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Summary Human AP endonuclease (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA. We used immunohistochemistry to examine the expression of HAP1 in normal breast and in 102 primary breast carcinomas. In normal breast epithelium, HAP1 had a uniformly nuclear localization. However, in lactating glandular epithelium, the expression of HAP1 was predominantly cytoplasmic. In carcinomas, both nuclear and cytoplasmic (44%), cytoplasmic (28%) or nuclear staining (24%) were observed. In four cases (4%), no HAP1 expression was detected. All patterns of expression for HAP1 were demonstrated for ductal carcinomas in situ (DCIS), although comedo-type DCIS were usually accompanied by mostly cytoplasmic staining. Similarly, the HAP1 expression in regions of invasive tumour necrosis was cytoplasmic. Pure nuclear HAP1 expression was significantly correlated with low angiogenesis (P = 0.007) and negative lymph node status (P = 0.001). In contrast, cases with cytoplasmic as well as nuclear staining were associated with poor prognostic factors, such as high angiogenesis (P = 0.03) and node positivity (P = 0.03). The pure nuclear staining may be related to better differentiation, as in normal breast, and hence better prognostic features, and cytoplasmic staining to a more metabolically active phenotype with high protein synthesis, as in lactating breast.Keywords: HAP1; breast cancer; immunohistochemistry; DNA repairThe DNA of all organisms, although inherently stable, is under constant threat from both endogenous and exogenous factors. The DNA repair process is of fundamental importance for the survival of all species, and recent studies have established the association of defective DNA repair machinery and cancer (Fishel et al, 1993;Leach et al, 1993).One of the most common lesions that arise in cellular DNA is the apurinic/apyrimidinic (AP) site, which results from the hydrolysis of the N-glycosyl bond linking the base to the deoxyribose moiety. AP sites are considered to be both cytotoxic and mutagenic, and they have been estimated to occur spontaneously at a rate of approximately 104 cell-' day-' from the mammalian cell genome (Loeb et al, 1986). Reactive oxygen species generated either during normal cellular metabolism or by exogenous agents, such as ionizing radiation, can increase this high error rate still further (Hutchinson, 1985;Teoule, 1987).There are specific DNA repair enzymes that recognize AP sites. The major human AP endonuclease (HAPI), also known as APE, APEX or Ref-1, is a 37-kDa protein that shows strong primary sequence similarity to Escherichia coli exonuclease III protein (Demple et al, 1991;Seki et al, 1991; Correspondence to: AL Harris residue is subsequently removed by a phosphodiesterase, followed by filling in of the nucleotide gap by DNA polymerase and DNA ligase, which seals the nick and permits the accurate progress of a DNA replication fork.Apart from its identification as a DNA repair protein, HAPI has been shown to regulate the reductive activation of oxidiz...

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The etiology of breast cancer characteristic alterations in hydroxyl radical-induced dna base lesions during oncogenesis with potential for evaluating incidence risk

Cited by 195 publications

References 25 publications

Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors

Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors

Cigarette Smoke Radicals and the Role of Free Radicals in Chemical Carcinogenicity

Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis

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