Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues

Mianying Wang, Kapil Dhingra, Walter N. Hittelman, Joachim G. Liehr, Mariza De Andrade, Donghui Li

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

The etiology of the majority of human breast cancers is unknown; however, oxidative stress and lipid peroxidation have been suggested to play a role in breast carcinogenesis. To address this possibility, DNA abducts induced by malondialdehyde (MDA), an end product of lipid peroxidation, were analyzed in surgical specimens of normal breast tissues of 51 breast cancer patients using the nuclease P1-enhanced version of the 32P-postlabeling assay. Normal breast tissue samples from 28 noncancer patients receiving reduction mammoplasty served as controls. Two previously characterized putative MDA deoxyadenosine (dA) and one MDA-deoxyguanosine adduct were detected in all tissue samples examined. Normal breast tissues from cancer patients exhibited significantly higher levels of the putative MDA abducts [median (42.5) and range (2.2-202.8) of relative adduct labeling x 109 values] than those found in noncancer controls (median, 15.67; range, 2.4- 382.1; P = 0.0001, Mann-Whitney U test). Ten of the 51 cancer patients and 1 of the 28 controls were found to contain the putative MDA abducts at the level of >1/107 nucleotides, a frequency comparable to that found in human liver. Age and body mass did not significantly influence the levels of these abducts. However, the presence of a previously detected benzo(a)pyrene-like DNA adduct in the breast tissues was associated with higher levels of the putative MDA-dA abducts in cancer patients (P = 0.012). The level of the putative MDA-dA abducts was significantly lower in smokers and former smokers compared to nonsmokers among cases after adjusting for age, body mass index, and status of the benzo(a)pyrene-like adduct (P = 0.009). Tumor tissues (n = 11) displayed significantly lower levels of the putative MDA abducts (median, 10.2; range, 5.3-20.6) than their corresponding normal adjacent tissues (median, 25.5; range, 10.5-13.8; P < 0.01). These findings provide evidence that lipid peroxidation products can accumulate in human breast tissues and reach relatively high levels in the breast tissues of women with breast cancer. There seems to be an interaction between these endogenous DNA modifications and carcinogen exposure-induced DNA abducts. Detection and quantitation of the putative MDA-DNA abducts may potentially be a useful tool in the understanding of breast cancer etiology.

Original languageEnglish (US)
Pages (from-to)705-710
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume5
Issue number9
StatePublished - Sep 1996
Externally publishedYes

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DNA Adducts
Malondialdehyde
Lipid Peroxidation
Breast
Breast Neoplasms
DNA
Neoplasms
Deoxyguanosine
Mammaplasty
Benzo(a)pyrene
Nonparametric Statistics
Carcinogens
Carcinogenesis
Oxidative Stress
Body Mass Index
Nucleotides
Liver

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. / Wang, Mianying; Dhingra, Kapil; Hittelman, Walter N.; Liehr, Joachim G.; De Andrade, Mariza; Li, Donghui.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 5, No. 9, 09.1996, p. 705-710.

Research output: Contribution to journalArticle

Wang, Mianying ; Dhingra, Kapil ; Hittelman, Walter N. ; Liehr, Joachim G. ; De Andrade, Mariza ; Li, Donghui. / Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. In: Cancer Epidemiology Biomarkers and Prevention. 1996 ; Vol. 5, No. 9. pp. 705-710.
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abstract = "The etiology of the majority of human breast cancers is unknown; however, oxidative stress and lipid peroxidation have been suggested to play a role in breast carcinogenesis. To address this possibility, DNA abducts induced by malondialdehyde (MDA), an end product of lipid peroxidation, were analyzed in surgical specimens of normal breast tissues of 51 breast cancer patients using the nuclease P1-enhanced version of the 32P-postlabeling assay. Normal breast tissue samples from 28 noncancer patients receiving reduction mammoplasty served as controls. Two previously characterized putative MDA deoxyadenosine (dA) and one MDA-deoxyguanosine adduct were detected in all tissue samples examined. Normal breast tissues from cancer patients exhibited significantly higher levels of the putative MDA abducts [median (42.5) and range (2.2-202.8) of relative adduct labeling x 109 values] than those found in noncancer controls (median, 15.67; range, 2.4- 382.1; P = 0.0001, Mann-Whitney U test). Ten of the 51 cancer patients and 1 of the 28 controls were found to contain the putative MDA abducts at the level of >1/107 nucleotides, a frequency comparable to that found in human liver. Age and body mass did not significantly influence the levels of these abducts. However, the presence of a previously detected benzo(a)pyrene-like DNA adduct in the breast tissues was associated with higher levels of the putative MDA-dA abducts in cancer patients (P = 0.012). The level of the putative MDA-dA abducts was significantly lower in smokers and former smokers compared to nonsmokers among cases after adjusting for age, body mass index, and status of the benzo(a)pyrene-like adduct (P = 0.009). Tumor tissues (n = 11) displayed significantly lower levels of the putative MDA abducts (median, 10.2; range, 5.3-20.6) than their corresponding normal adjacent tissues (median, 25.5; range, 10.5-13.8; P < 0.01). These findings provide evidence that lipid peroxidation products can accumulate in human breast tissues and reach relatively high levels in the breast tissues of women with breast cancer. There seems to be an interaction between these endogenous DNA modifications and carcinogen exposure-induced DNA abducts. Detection and quantitation of the putative MDA-DNA abducts may potentially be a useful tool in the understanding of breast cancer etiology.",
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