This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, D. Articles by Hittelman, W. N. Search for Related Content PubMed PubMed Citation Articles by Li, D. Articles by Hittelman, W. N.

Aromatic DNA Adducts in Adjacent Tissues of Breast Cancer Patients: Clues to Breast Cancer Etiology¹

Departments of Clinical Investigations [D. L., M. W., W. N. H.] and Breast Medical Oncology [K. D.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

The etiology of the majority of human breast cancers is unknown. Environmental factors have long been suspected to play a role, but no specific causative agent has been identified. If the hypothesis that environmental carcinogen exposure contributes to human breast cancer is true, carcinogen-DNA adducts would be expected to be present in human breast tissues. To address this possibility, aromatic DNA adducts were measured in 87 surgical specimens of normal human breast tissues from 87 breast cancer patients undergoing mastectomy using the nuclease P1-enhanced version of the ³²P postlabeling assay. Breast tissue samples from 29 noncancer patients undergoing reduction mammoplasty served as controls. Whereas aromatic DNA adducts were detected in all tissue samples examined, the total adduct levels in cancer patients were significantly higher than that in noncancer controls [mean ± SEM, 97.4 ± 23.4/10⁹ nucleotides (range, 3.8–1737.1) versus 18.1 ± 11.6/10⁹ nucleotides (range, 5.6–56.7), respectively; P < 0.01, t test and Mann-Whitney test]. This difference was not affected by the age distribution of the two groups. The typical smoking-related DNA adduct pattern (i.e., a diagonal radioactive zone) was observed in 29 of 87 tissues (17 of 17 current smokers, 5 of 8 former smokers, 4 of 52 nonsmokers, and 3 of 10 patients with unknown smoking status) and in 2 of 10 control tissues. It was of interest that a benzo(a)pyrene (BP)-like DNA adduct was observed in 36 normal adjacent breast tissues (41%), 27 of which were from nonsmokers. Levels of this BP-like adduct were extremely high (> 100/10⁹ nucleotides) in 5 patients (4 nonsmokers and 1 smoker) and moderately high (> 10/10⁹ nucleotides) in 13 other patients (8 nonsmokers and 5 smokers). One patient exhibited this adduct at a level of 1500/10⁹ nucleotides, which is comparable to the highest level of total adducts reported in human tissues related to carcinogen exposure (e.g., cigarette smoking). In contrast, this adduct was absent (<1/10¹⁰ nucleotides) in all of the control tissues. Cochromatography and rechromatography analysis of DNA samples from human breast tissues and from MCF-7 cells treated with BP revealed that this adduct could be generated by BP exposure but is not the major BP 7,8-diol-9,10-epoxide-deoxyguanine adduct detected previously in animal tissues and human mammary epithelial cells. These findings support the hypothesis that environmental carcinogen exposure, in addition to cigarette smoking, may be associated with the etiology of human breast cancer.

¹ This investigation was supported by a grant from University of Texas M. D. Anderson Cancer Center Physicians Referral Service.

² To whom requests for reprints should be addressed, at Department of Clinical Investigation. Box 019. University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 7/27/95. Accepted 11/ 7/95.

This article has been cited by other articles:

				S. Rohrmann, S.-U. Lukas Jung, J. Linseisen, and W. Pfau Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue Mutagenesis, November 2, 2008; (2008) gen058v1. [Abstract] [Full Text] [PDF]

				H. Zhao, L.-E Wang, D. Li, R. M. Chamberlain, E. M. Sturgis, and Q. Wei Genotypes and haplotypes of ERCC1 and ERCC2/XPD genes predict levels of benzo[a]pyrene diol epoxide-induced DNA adducts in cultured primary lymphocytes from healthy individuals: a genotype-phenotype correlation analysis Carcinogenesis, August 1, 2008; 29(8): 1560 - 1566. [Abstract] [Full Text] [PDF]

				F. Wang, D. Chang, F.-l. Hu, H. Sui, B. Han, D.-d. li, and Y.-s. Zhao DNA Repair Gene XPD Polymorphisms and Cancer Risk: A Meta-analysis Based on 56 Case-Control Studies Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 507 - 517. [Abstract] [Full Text] [PDF]

				D. H. Phillips and S. Garte Smoking and Breast Cancer: Is There Really a Link? Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 1 - 2. [Full Text] [PDF]

				K. D. Crew, M. D. Gammon, M. B. Terry, F. F. Zhang, M. Agrawal, S. M. Eng, S. K. Sagiv, S. L. Teitelbaum, A. I. Neugut, and R. M. Santella Genetic polymorphisms in the apoptosis-associated genes FAS and FASL and breast cancer risk Carcinogenesis, December 1, 2007; 28(12): 2548 - 2551. [Abstract] [Full Text] [PDF]

				K. D. Crew, M. D. Gammon, M. B. Terry, F. F. Zhang, L. B. Zablotska, M. Agrawal, J. Shen, C.-M. Long, S. M. Eng, S. K. Sagiv, et al. Polymorphisms in Nucleotide Excision Repair Genes, Polycyclic Aromatic Hydrocarbon-DNA Adducts, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 2033 - 2041. [Abstract] [Full Text] [PDF]

				C. Bradley, R. van der Meer, N. Roodi, H. Yan, M. B. Chandrasekharan, Z.-W. Sun, R. L. Mernaugh, and F. F. Parl Carcinogen-induced histone alteration in normal human mammary epithelial cells Carcinogenesis, October 1, 2007; 28(10): 2184 - 2192. [Abstract] [Full Text] [PDF]

				M. Prince, C. T. Campbell, T. A. Robertson, A. J. Wells, and H. E. Kleiner Naturally occurring coumarins inhibit 7,12-dimethylbenz[a]anthracene DNA adduct formation in mouse mammary gland Carcinogenesis, June 1, 2006; 27(6): 1204 - 1213. [Abstract] [Full Text] [PDF]

				X. Wen and T. Walle Preferential induction of CYP1B1 by benzo[a]pyrene in human oral epithelial cells: impact on DNA adduct formation and prevention by polyphenols Carcinogenesis, October 1, 2005; 26(10): 1774 - 1781. [Abstract] [Full Text] [PDF]

				L. F. Masson, L. Sharp, S. C. Cotton, and J. Little Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review Am. J. Epidemiol., May 15, 2005; 161(10): 901 - 915. [Abstract] [Full Text] [PDF]

				J.-H. Yoon, A. Besaratinia, Z. Feng, M.-s. Tang, S. Amin, A. Luch, and G. P. Pfeifer DNA Damage, Repair, and Mutation Induction by (+)-Syn and (-)-Anti-Dibenzo[a,l]Pyrene-11,12-Diol-13,14-Epoxides in Mouse Cells Cancer Res., October 15, 2004; 64(20): 7321 - 7328. [Abstract] [Full Text] [PDF]

				Q. Shi, L.-E. Wang, M. L. Bondy, A. Brewster, S. E. Singletary, and Q. Wei Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients Carcinogenesis, September 1, 2004; 25(9): 1695 - 1700. [Abstract] [Full Text] [PDF]

				T. Boyiri, J. Guttenplan, M. Khmelnitsky, W. Kosinska, J.-M. Lin, D. Desai, S. Amin, B. Pittman, and K. El-Bayoumy Mammary carcinogenesis and molecular analysis of in vivo cII gene mutations in the mammary tissue of female transgenic rats treated with the environmental pollutant 6-nitrochrysene Carcinogenesis, April 1, 2004; 25(4): 637 - 643. [Abstract] [Full Text] [PDF]

				T. R. Smith, M. S. Miller, K. K. Lohman, L.D. Case, and J. J. Hu DNA damage and breast cancer risk Carcinogenesis, May 1, 2003; 24(5): 883 - 889. [Abstract] [Full Text] [PDF]

				B. Faraglia, S. Y. Chen, M. D. Gammon, Y. Zhang, S. L. Teitelbaum, A. I. Neugut, H. Ahsan, G. C. Garbowski, H. Hibshoosh, D. Lin, et al. Evaluation of 4-aminobiphenyl-DNA adducts in human breast cancer: the influence of tobacco smoke Carcinogenesis, April 1, 2003; 24(4): 719 - 725. [Abstract] [Full Text] [PDF]

				M. D. Gammon and R. M. Santella Reply Cancer Epidemiol. Biomarkers Prev., January 1, 2003; 12(1): 75-A - 76. [Full Text] [PDF]

				D. H. Phillips Smoking-related DNA and protein adducts in human tissues Carcinogenesis, December 1, 2002; 23(12): 1979 - 2004. [Abstract] [Full Text] [PDF]

				P. D. Terry and T. E. Rohan Cigarette Smoking and the Risk of Breast Cancer in Women: A Review of the Literature Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 953 - 971. [Abstract] [Full Text] [PDF]

				D. Li, F. L. Walcott, P. Chang, W. Zhang, J. Zhu, E. Petrulis, S. E. Singletary, A. A. Sahin, and M. L. Bondy Genetic and Environmental Determinants on Tissue Response to in Vitro Carcinogen Exposure and Risk of Breast Cancer Cancer Res., August 15, 2002; 62(16): 4566 - 4570. [Abstract] [Full Text] [PDF]

				M. D. Gammon, R. M. Santella, A. I. Neugut, S. M. Eng, S. L. Teitelbaum, A. Paykin, B. Levin, M. B. Terry, T. L. Young, L. W. Wang, et al. Environmental Toxins and Breast Cancer on Long Island. I. Polycyclic Aromatic Hydrocarbon DNA Adducts Cancer Epidemiol. Biomarkers Prev., August 1, 2002; 11(8): 677 - 685. [Abstract] [Full Text] [PDF]

				K. Conway, S. N. Edmiston, L. Cui, S. S. Drouin, J. Pang, M. He, C.-K. Tse, J. Geradts, L. Dressler, E. T. Liu, et al. Prevalence and Spectrum of p53 Mutations Associated with Smoking in Breast Cancer Cancer Res., April 1, 2002; 62(7): 1987 - 1995. [Abstract] [Full Text] [PDF]

				N. Guo, D. V. Faller, and C. Vaziri Carcinogen-induced S-Phase Arrest Is Chk1 Mediated and Caffeine Sensitive Cell Growth Differ., February 1, 2002; 13(2): 77 - 86. [Abstract] [Full Text] [PDF]

				P. F. Firozi, M. L. Bondy, A. A. Sahin, P. Chang, F. Lukmanji, E. S. Singletary, M. M. Hassan, and D. Li Aromatic DNA adducts and polymorphisms of CYP1A1, NAT2, and GSTM1 in breast cancer Carcinogenesis, February 1, 2002; 23(2): 301 - 306. [Abstract] [Full Text] [PDF]

				P. Xiong, M. L. Bondy, D. Li, H. Shen, L.-E Wang, S. E. Singletary, M. R. Spitz, and Q. Wei Sensitivity to Benzo(a)pyrene Diol-Epoxide Associated with Risk of Breast Cancer in Young Women and Modulation by Glutathione S-Transferase Polymorphisms: A Case-Control Study Cancer Res., December 1, 2001; 61(23): 8465 - 8469. [Abstract] [Full Text] [PDF]

				K. W. Singletary and S. M. Gapstur Alcohol and Breast Cancer: Review of Epidemiologic and Experimental Evidence and Potential Mechanisms JAMA, November 7, 2001; 286(17): 2143 - 2151. [Abstract] [Full Text] [PDF]

				F. L. Martin Genotoxins and the initiation of sporadic breast cancer Mutagenesis, March 1, 2001; 16(2): 155 - 161. [Abstract] [Full Text] [PDF]

				R. Goth-Goldstein, M. R. Stampfer, C. A. Erdmann, and M. Russell Interindividual variation in CYP1A1 expression in breast tissue and the role of genetic polymorphism Carcinogenesis, November 1, 2000; 21(11): 2119 - 2122. [Abstract] [Full Text] [PDF]

				S. L. Barnes, K. W. Singletary, and R. Frey Ethanol and acetaldehyde enhance benzo[a]pyrene-DNA adduct formation in human mammary epithelial cells Carcinogenesis, November 1, 2000; 21(11): 2123 - 2128. [Full Text] [PDF]

				A. Rundle, D. Tang, J. Zhou, S. Cho, and F. Perera The Association between Glutathione S-Transferase M1 Genotype and Polycyclic Aromatic Hydrocarbon-DNA Adducts in Breast Tissue Cancer Epidemiol. Biomarkers Prev., October 1, 2000; 9(10): 1079 - 1085. [Abstract] [Full Text]

				J. A. Williams and D. H. Phillips Mammary Expression of Xenobiotic Metabolizing Enzymes and Their Potential Role in Breast Cancer Cancer Res., September 1, 2000; 60(17): 4667 - 4677. [Abstract] [Full Text]

				A. Rundle, D. Tang, H. Hibshoosh, A. Estabrook, F. Schnabel, W. Cao, S. Grumet, and F. P. Perera The relationship between genetic damage from polycyclic aromatic hydrocarbons in breast tissue and breast cancer Carcinogenesis, July 1, 2000; 21(7): 1281 - 1289. [Abstract] [Full Text] [PDF]

				T. A. Lallas, S. K. McClain, M. S. Shahin, and R. E. Buller The Glutathione S-Transferase M1 Genotype in Ovarian Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 2000; 9(6): 587 - 590. [Abstract] [Full Text]

				F. P. Perera Molecular Epidemiology: On the Path to Prevention? J Natl Cancer Inst, April 19, 2000; 92(8): 602 - 612. [Abstract] [Full Text] [PDF]

				N. Guo, D. V. Faller, and C. Vaziri A Novel DNA Damage Checkpoint Involving Post-transcriptional Regulation of Cyclin A Expression J. Biol. Chem., January 21, 2000; 275(3): 1715 - 1722. [Abstract] [Full Text] [PDF]

				C.-L. Chen, C.-W. Chi, K.-W. Chang, and T.-Y. Liu Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history Carcinogenesis, December 1, 1999; 20(12): 2331 - 2334. [Abstract] [Full Text] [PDF]