Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2001 Jul;109(7):739–747. doi: 10.1289/ehp.01109739

Modulatory effects of neonatal exposure to TCDD, or a mixture of PCBs, p,p'-DDT, and p-p'-DDE, on methylnitrosourea-induced mammary tumor development in the rat.

D Desaulniers 1, K Leingartner 1, J Russo 1, G Perkins 1, B G Chittim 1, M C Archer 1, M Wade 1, J Yang 1
PMCID: PMC1240379  PMID: 11485874

Abstract

The role of organochlorine (OC) exposure in the etiology of breast cancer remains controversial. Thus, our objective was to determine whether the most abundant and toxic OCs found in human milk could, when ingested during the neonatal period, modulate the development of mammary tumors in the rat. We prepared a mixture composed of p,p'-dichlorodiphenyltrichloroethane (DDT), its major metabolite, p,p'-dichlorodiphenyldichloroethene (DDE), and 19 polychlorinated biphenyls (PCB) based on their concentrations found in the milk of Canadian women. Neonate rats at 1, 5, 10, 15, and 20 days of age were gavaged with this mixture, at 10, 100, and 1,000 times the amount that a human baby would consume. An additional group received 2.5 microg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg body weight (bw) by gavage at 18 days of age, instead of the mixture. On day 21, all treatment groups, except for a control group and a 1,000-mix group, received a single intraperitoneal injection of methylnitrosourea (MNU, 30 mg/kg bw), the initiator of the carcinogenic process. The average number of rats per treatment group was 33. Rats were sacrificed when their tumors reached 1 cm in size, or at 308 days of age. We prepared mammary tumors and mammary gland whole mounts for histologic analysis. There were no significant effects when only the malignant or only the benign tumors were considered. After all benign and malignant lesions were pooled, the number of mammary tumors differed among all MNU-treated groups (p = 0.02) with more lesions developing in the MNU-1,000[times] (median = 4.5; p = 0.05) and MNU-TCDD (median = 5.5; p = 0.07) compared to the MNU-0 rats (median = 2). Compared to the MNU-0 group, the percentage of rats that developed palpable tumors (benign plus malignant) was slightly higher (p = 0.06) in the MNU-TCDD group, but not in the MNU-1,000[times] group. The percentage of palpable tumors that were malignant was higher (p = 0.02) in the MNU-100[times] group (15/16, 94%) than in the MNU-0 group (10/18, 56%). The highest dose of the mixture delayed (p = 0.03) the development of tumors, but this was not observed with the MNU-TCDD treatment. These results suggest that neonatal exposure to high doses of organochlorines could favor the development of MNU-induced mammary lesions, but also delays the development of palpable tumors in the rat.

Full Text

The Full Text of this article is available as a PDF (159.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson K. J., Miller A. B., Woolcott C. G., Sterns E. E., McCready D. R., Lickley L. A., Fish E. B., Hiraki G. Y., Holloway C., Ross T. Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2000 Jan;9(1):55–63. [PubMed] [Google Scholar]
  2. Barter R. A., Klaassen C. D. Reduction of thyroid hormone levels and alteration of thyroid function by four representative UDP-glucuronosyltransferase inducers in rats. Toxicol Appl Pharmacol. 1994 Sep;128(1):9–17. doi: 10.1006/taap.1994.1174. [DOI] [PubMed] [Google Scholar]
  3. Bartsch H., Nair U., Risch A., Rojas M., Wikman H., Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev. 2000 Jan;9(1):3–28. [PubMed] [Google Scholar]
  4. Bertazzi P. A., Bernucci I., Brambilla G., Consonni D., Pesatori A. C. The Seveso studies on early and long-term effects of dioxin exposure: a review. Environ Health Perspect. 1998 Apr;106 (Suppl 2):625–633. doi: 10.1289/ehp.98106625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brouwer A., Morse D. C., Lans M. C., Schuur A. G., Murk A. J., Klasson-Wehler E., Bergman A., Visser T. J. Interactions of persistent environmental organohalogens with the thyroid hormone system: mechanisms and possible consequences for animal and human health. Toxicol Ind Health. 1998 Jan-Apr;14(1-2):59–84. doi: 10.1177/074823379801400107. [DOI] [PubMed] [Google Scholar]
  6. Burow M. E., Tang Y., Collins-Burow B. M., Krajewski S., Reed J. C., McLachlan J. A., Beckman B. S. Effects of environmental estrogens on tumor necrosis factor alpha-mediated apoptosis in MCF-7 cells. Carcinogenesis. 1999 Nov;20(11):2057–2061. doi: 10.1093/carcin/20.11.2057. [DOI] [PubMed] [Google Scholar]
  7. Cha R. S., Guerra L., Thilly W. G., Zarbl H. Ha-ras-1 oncogene mutations in mammary epithelial cells do not contribute to initiation of spontaneous mammary tumorigenesis in rats. Carcinogenesis. 1996 Nov;17(11):2519–2524. doi: 10.1093/carcin/17.11.2519. [DOI] [PubMed] [Google Scholar]
  8. Cha R. S., Thilly W. G., Zarbl H. N-nitroso-N-methylurea-induced rat mammary tumors arise from cells with preexisting oncogenic Hras1 gene mutations. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3749–3753. doi: 10.1073/pnas.91.9.3749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cocco P., Kazerouni N., Zahm S. H. Cancer mortality and environmental exposure to DDE in the United States. Environ Health Perspect. 2000 Jan;108(1):1–4. doi: 10.1289/ehp.001081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coggon D., Kellingray S., Inskip H., Croft P., Campbell L., Cooper C. Osteoarthritis of the hip and occupational lifting. Am J Epidemiol. 1998 Mar 15;147(6):523–528. doi: 10.1093/oxfordjournals.aje.a009483. [DOI] [PubMed] [Google Scholar]
  11. Craan A. G., Haines D. A. Twenty-five years of surveillance for contaminants in human breast milk. Arch Environ Contam Toxicol. 1998 Nov;35(4):702–710. doi: 10.1007/s002449900434. [DOI] [PubMed] [Google Scholar]
  12. Darnerud P. O., Sinjari T., Jönsson C. J. Foetal uptake of coplanar polychlorinated biphenyl (PCB) congeners in mice. Pharmacol Toxicol. 1996 Mar;78(3):187–192. doi: 10.1111/j.1600-0773.1996.tb00202.x. [DOI] [PubMed] [Google Scholar]
  13. Davis D. L., Bradlow H. L., Wolff M., Woodruff T., Hoel D. G., Anton-Culver H. Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ Health Perspect. 1993 Oct;101(5):372–377. doi: 10.1289/ehp.93101372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Davis D. L., Telang N. T., Osborne M. P., Bradlow H. L. Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer. Environ Health Perspect. 1997 Apr;105 (Suppl 3):571–576. doi: 10.1289/ehp.97105s3571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Davis J. W., 2nd, Melendez K., Salas V. M., Lauer F. T., Burchiel S. W. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits growth factor withdrawal-induced apoptosis in the human mammary epithelial cell line, MCF-10A. Carcinogenesis. 2000 May;21(5):881–886. doi: 10.1093/carcin/21.5.881. [DOI] [PubMed] [Google Scholar]
  16. Dewailly E., Dodin S., Verreault R., Ayotte P., Sauvé L., Morin J., Brisson J. High organochlorine body burden in women with estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1994 Feb 2;86(3):232–234. doi: 10.1093/jnci/86.3.232. [DOI] [PubMed] [Google Scholar]
  17. Dunning A. M., Healey C. S., Pharoah P. D., Teare M. D., Ponder B. A., Easton D. F. A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1999 Oct;8(10):843–854. [PubMed] [Google Scholar]
  18. Ekbom A., Hsieh C. C., Lipworth L., Adami H. Q., Trichopoulos D. Intrauterine environment and breast cancer risk in women: a population-based study. J Natl Cancer Inst. 1997 Jan 1;89(1):71–76. doi: 10.1093/jnci/89.1.71. [DOI] [PubMed] [Google Scholar]
  19. Engelbergs J., Thomale J., Galhoff A., Rajewsky M. F. Fast repair of O6-ethylguanine, but not O6-methylguanine, in transcribed genes prevents mutation of H-ras in rat mammary tumorigenesis induced by ethylnitrosourea in place of methylnitrosourea. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1635–1640. doi: 10.1073/pnas.95.4.1635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Falck F., Jr, Ricci A., Jr, Wolff M. S., Godbold J., Deckers P. Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer. Arch Environ Health. 1992 Mar-Apr;47(2):143–146. [PubMed] [Google Scholar]
  21. Frank R., Rasper J., Smout M. S., Braun H. E. Organochlorine residues in adipose tissues, blood and milk from Ontario residents, 1976-1985. Can J Public Health. 1988 May-Jun;79(3):150–158. [PubMed] [Google Scholar]
  22. Hardell L., Lindström G., Liljegren G., Dahl P., Magnuson A. Increased concentrations of octachlorodibenzo-p-dioxin in cases with breast cancer--results from a case-control study. Eur J Cancer Prev. 1996 Oct;5(5):351–357. doi: 10.1097/00008469-199610000-00007. [DOI] [PubMed] [Google Scholar]
  23. Helzlsouer K. J., Alberg A. J., Huang H. Y., Hoffman S. C., Strickland P. T., Brock J. W., Burse V. W., Needham L. L., Bell D. A., Lavigne J. A. Serum concentrations of organochlorine compounds and the subsequent development of breast cancer. Cancer Epidemiol Biomarkers Prev. 1999 Jun;8(6):525–532. [PubMed] [Google Scholar]
  24. Hilakivi-Clarke L., Stoica A., Raygada M., Martin M. B. Consumption of a high-fat diet alters estrogen receptor content, protein kinase C activity, and mammary gland morphology in virgin and pregnant mice and female offspring. Cancer Res. 1998 Feb 15;58(4):654–660. [PubMed] [Google Scholar]
  25. Hoivik D., Willett K., Wilson C., Safe S. Estrogen does not inhibit 2,3,7, 8-tetrachlorodibenzo-p-dioxin-mediated effects in MCF-7 and Hepa 1c1c7 cells. J Biol Chem. 1997 Nov 28;272(48):30270–30274. doi: 10.1074/jbc.272.48.30270. [DOI] [PubMed] [Google Scholar]
  26. Holcomb M., Safe S. Inhibition of 7,12-dimethylbenzanthracene-induced rat mammary tumor growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cancer Lett. 1994 Jul 15;82(1):43–47. doi: 10.1016/0304-3835(94)90144-9. [DOI] [PubMed] [Google Scholar]
  27. Hsieh S. F., Yen Y. Y., Lan S. J., Hsieh C. C., Lee C. H., Ko Y. C. A cohort study on mortality and exposure to polychlorinated biphenyls. Arch Environ Health. 1996 Nov-Dec;51(6):417–424. doi: 10.1080/00039896.1996.9936040. [DOI] [PubMed] [Google Scholar]
  28. Hunter D. J., Hankinson S. E., Laden F., Colditz G. A., Manson J. E., Willett W. C., Speizer F. E., Wolff M. S. Plasma organochlorine levels and the risk of breast cancer. N Engl J Med. 1997 Oct 30;337(18):1253–1258. doi: 10.1056/NEJM199710303371801. [DOI] [PubMed] [Google Scholar]
  29. Iida T., Hirakawa H., Matsueda T., Takenaka S., Yu M. L., Guo Y. L. Recent trend of polychlorinated dibenzo-p-dioxins and their related compounds in the blood and sebum of Yusho and Yu Cheng patients. Chemosphere. 1999 Feb;38(5):981–993. doi: 10.1016/s0045-6535(98)00360-9. [DOI] [PubMed] [Google Scholar]
  30. Jansen H. T., Cooke P. S., Porcelli J., Liu T. C., Hansen L. G. Estrogenic and antiestrogenic actions of PCBs in the female rat: in vitro and in vivo studies. Reprod Toxicol. 1993 May-Jun;7(3):237–248. doi: 10.1016/0890-6238(93)90230-5. [DOI] [PubMed] [Google Scholar]
  31. Kannan N., Tanabe S., Tatsukawa R. Potentially hazardous residues of non-ortho chlorine substituted coplanar PCBs in human adipose tissue. Arch Environ Health. 1988 Jan-Feb;43(1):11–14. doi: 10.1080/00039896.1988.9934366. [DOI] [PubMed] [Google Scholar]
  32. Kociba R. J., Keyes D. G., Beyer J. E., Carreon R. M., Wade C. E., Dittenber D. A., Kalnins R. P., Frauson L. E., Park C. N., Barnard S. D. Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol Appl Pharmacol. 1978 Nov;46(2):279–303. doi: 10.1016/0041-008x(78)90075-3. [DOI] [PubMed] [Google Scholar]
  33. Krieger N., Wolff M. S., Hiatt R. A., Rivera M., Vogelman J., Orentreich N. Breast cancer and serum organochlorines: a prospective study among white, black, and Asian women. J Natl Cancer Inst. 1994 Apr 20;86(8):589–599. doi: 10.1093/jnci/86.8.589. [DOI] [PubMed] [Google Scholar]
  34. Lichtenstein P., Holm N. V., Verkasalo P. K., Iliadou A., Kaprio J., Koskenvuo M., Pukkala E., Skytthe A., Hemminki K. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000 Jul 13;343(2):78–85. doi: 10.1056/NEJM200007133430201. [DOI] [PubMed] [Google Scholar]
  35. Liljegren G., Hardell L., Lindström G., Dahl P., Magnuson A. Case-control study on breast cancer and adipose tissue concentrations of congener specific polychlorinated biphenyls, DDE and hexachlorobenzene. Eur J Cancer Prev. 1998 Apr;7(2):135–140. [PubMed] [Google Scholar]
  36. Lu J., Jiang C., Mitrenga T., Cutter G., Thompson H. J. Pathogenic characterization of 1-methyl-1-nitrosourea-induced mammary carcinomas in the rat. Carcinogenesis. 1998 Jan;19(1):223–227. doi: 10.1093/carcin/19.1.223. [DOI] [PubMed] [Google Scholar]
  37. Lu S. J., Archer M. C. Ha-ras oncogene activation in mammary glands of N-methyl-N-nitrosourea-treated rats genetically resistant to mammary adenocarcinogenesis. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1001–1005. doi: 10.1073/pnas.89.3.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. López-Carrillo L., Blair A., López-Cervantes M., Cebrián M., Rueda C., Reyes R., Mohar A., Bravo J. Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico. Cancer Res. 1997 Sep 1;57(17):3728–3732. [PubMed] [Google Scholar]
  39. Madigan M. P., Ziegler R. G., Benichou J., Byrne C., Hoover R. N. Proportion of breast cancer cases in the United States explained by well-established risk factors. J Natl Cancer Inst. 1995 Nov 15;87(22):1681–1685. doi: 10.1093/jnci/87.22.1681. [DOI] [PubMed] [Google Scholar]
  40. McDougal A., Wilson C., Safe S. Inhibition of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor growth by aryl hydrocarbon receptor agonists. Cancer Lett. 1997 Nov 25;120(1):53–63. doi: 10.1016/s0304-3835(97)00299-1. [DOI] [PubMed] [Google Scholar]
  41. Mes J., Davies D. J., Doucet J., Weber D., McMullen E. Levels of chlorinated hydrocarbon residues in Canadian human breast milk and their relationship to some characteristics of the donors. Food Addit Contam. 1993 Jul-Aug;10(4):429–441. doi: 10.1080/02652039309374166. [DOI] [PubMed] [Google Scholar]
  42. Mezzetti M., La Vecchia C., Decarli A., Boyle P., Talamini R., Franceschi S. Population attributable risk for breast cancer: diet, nutrition, and physical exercise. J Natl Cancer Inst. 1998 Mar 4;90(5):389–394. doi: 10.1093/jnci/90.5.389. [DOI] [PubMed] [Google Scholar]
  43. Moysich K. B., Ambrosone C. B., Vena J. E., Shields P. G., Mendola P., Kostyniak P., Greizerstein H., Graham S., Marshall J. R., Schisterman E. F. Environmental organochlorine exposure and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1998 Mar;7(3):181–188. [PubMed] [Google Scholar]
  44. Moysich K. B., Shields P. G., Freudenheim J. L., Schisterman E. F., Vena J. E., Kostyniak P., Greizerstein H., Marshall J. R., Graham S., Ambrosone C. B. Polychlorinated biphenyls, cytochrome P4501A1 polymorphism, and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1999 Jan;8(1):41–44. [PubMed] [Google Scholar]
  45. Murray F. J., Smith F. A., Nitschke K. D., Humiston C. G., Kociba R. J., Schwetz B. A. Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet. Toxicol Appl Pharmacol. 1979 Sep 15;50(2):241–252. doi: 10.1016/0041-008x(79)90149-2. [DOI] [PubMed] [Google Scholar]
  46. Mussalo-Rauhamaa H., Häsänen E., Pyysalo H., Antervo K., Kauppila R., Pantzar P. Occurrence of beta-hexachlorocyclohexane in breast cancer patients. Cancer. 1990 Nov 15;66(10):2124–2128. doi: 10.1002/1097-0142(19901115)66:10<2124::aid-cncr2820661014>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  47. Nakamura J., Savinov A., Lu Q., Brodie A. Estrogen regulates vascular endothelial growth/permeability factor expression in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. Endocrinology. 1996 Dec;137(12):5589–5596. doi: 10.1210/endo.137.12.8940388. [DOI] [PubMed] [Google Scholar]
  48. Nesaretnam K., Hales E., Sohail M., Krausz T., Darbre P. 3,3',4,4'-tetrachlorobiphenyl (TCB) can enhance DMBA-induced mammary carcinogenesis in the rat. Eur J Cancer. 1998 Feb;34(3):389–393. doi: 10.1016/s0959-8049(97)10026-0. [DOI] [PubMed] [Google Scholar]
  49. Newsome W. H., Davies D. Determination of PCB metabolites in Canadian human milk. Chemosphere. 1996 Aug;33(3):559–565. doi: 10.1016/0045-6535(96)00199-3. [DOI] [PubMed] [Google Scholar]
  50. Porterfield S. P., Hendry L. B. Impact of PCBs on thyroid hormone directed brain development. Toxicol Ind Health. 1998 Jan-Apr;14(1-2):103–120. doi: 10.1177/074823379801400109. [DOI] [PubMed] [Google Scholar]
  51. Ramamoorthy K., Gupta M. S., Sun G., McDougal A., Safe S. H. 3,3'4,4'-Tetrachlorobiphenyl exhibits antiestrogenic and antitumorigenic activity in the rodent uterus and mammary cells and in human breast cancer cells. Carcinogenesis. 1999 Jan;20(1):115–123. doi: 10.1093/carcin/20.1.115. [DOI] [PubMed] [Google Scholar]
  52. Ries L. A., Wingo P. A., Miller D. S., Howe H. L., Weir H. K., Rosenberg H. M., Vernon S. W., Cronin K., Edwards B. K. The annual report to the nation on the status of cancer, 1973-1997, with a special section on colorectal cancer. Cancer. 2000 May 15;88(10):2398–2424. doi: 10.1002/(sici)1097-0142(20000515)88:10<2398::aid-cncr26>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  53. Robison A. K., Sirbasku D. A., Stancel G. M. DDT supports the growth of an estrogen-responsive tumor. Toxicol Lett. 1985 Sep;27(1-3):109–113. doi: 10.1016/0378-4274(85)90127-4. [DOI] [PubMed] [Google Scholar]
  54. Russo I. H., Russo J. Mammary gland neoplasia in long-term rodent studies. Environ Health Perspect. 1996 Sep;104(9):938–967. doi: 10.1289/ehp.96104938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Russo J., Gusterson B. A., Rogers A. E., Russo I. H., Wellings S. R., van Zwieten M. J. Comparative study of human and rat mammary tumorigenesis. Lab Invest. 1990 Mar;62(3):244–278. [PubMed] [Google Scholar]
  56. Russo J., Russo I. H. Biological and molecular bases of mammary carcinogenesis. Lab Invest. 1987 Aug;57(2):112–137. [PubMed] [Google Scholar]
  57. Safe S. H. Environmental and dietary estrogens and human health: is there a problem? Environ Health Perspect. 1995 Apr;103(4):346–351. doi: 10.1289/ehp.95103346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Safe S. H. Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. Pharmacol Ther. 1995;67(2):247–281. doi: 10.1016/0163-7258(95)00017-b. [DOI] [PubMed] [Google Scholar]
  59. Safe S. H. Xenoestrogens and breast cancer. N Engl J Med. 1997 Oct 30;337(18):1303–1304. doi: 10.1056/NEJM199710303371809. [DOI] [PubMed] [Google Scholar]
  60. Safe S. Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds. Teratog Carcinog Mutagen. 1997;17(4-5):285–304. [PubMed] [Google Scholar]
  61. Safe S. Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). Crit Rev Toxicol. 1990;21(1):51–88. doi: 10.3109/10408449009089873. [DOI] [PubMed] [Google Scholar]
  62. Sakorafas G. H., Tsiotou A. G. Genetic predisposition to breast cancer: a surgical perspective. Br J Surg. 2000 Feb;87(2):149–162. doi: 10.1046/j.1365-2168.2000.01347.x. [DOI] [PubMed] [Google Scholar]
  63. Sanderson M., Williams M. A., Malone K. E., Stanford J. L., Emanuel I., White E., Daling J. R. Perinatal factors and risk of breast cancer. Epidemiology. 1996 Jan;7(1):34–37. doi: 10.1097/00001648-199601000-00007. [DOI] [PubMed] [Google Scholar]
  64. Schrenk D. Impact of dioxin-type induction of drug-metabolizing enzymes on the metabolism of endo- and xenobiotics. Biochem Pharmacol. 1998 Apr 15;55(8):1155–1162. doi: 10.1016/s0006-2952(97)00591-1. [DOI] [PubMed] [Google Scholar]
  65. Shirai K., Uemura Y., Fukumoto M., Tsukamoto T., Pascual R., Nandi S., Tsubura A. Synergistic effect of MNU and DMBA in mammary carcinogenesis and H-ras activation in female Sprague-Dawley rats. Cancer Lett. 1997 Nov 25;120(1):87–93. doi: 10.1016/s0304-3835(97)00293-0. [DOI] [PubMed] [Google Scholar]
  66. Silinskas K. C., Okey A. B. Protection by 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) against mammary tumors and leukemia during prolonged feeding of 7,12-dimethylbenz(a)anthracene to female rats. J Natl Cancer Inst. 1975 Sep;55(3):653–657. doi: 10.1093/jnci/55.3.653. [DOI] [PubMed] [Google Scholar]
  67. Sinjari T., Klasson-Wehler E., Oskarsson A., Darnerud P. O. Milk transfer and neonatal uptake of coplanar polychlorinated biphenyl (PCB) congeners in mice. Pharmacol Toxicol. 1996 Mar;78(3):181–186. doi: 10.1111/j.1600-0773.1996.tb00201.x. [DOI] [PubMed] [Google Scholar]
  68. Soto A. M., Sonnenschein C., Chung K. L., Fernandez M. F., Olea N., Serrano F. O. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect. 1995 Oct;103 (Suppl 7):113–122. doi: 10.1289/ehp.95103s7113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Sukumar S., McKenzie K., Chen Y. Animal models for breast cancer. Mutat Res. 1995 Dec;333(1-2):37–44. doi: 10.1016/0027-5107(95)00129-8. [DOI] [PubMed] [Google Scholar]
  70. Tavani A., Braga C., La Vecchia C., Negri E., Russo A., Franceschi S. Attributable risks for breast cancer in Italy: education, family history and reproductive and hormonal factors. Int J Cancer. 1997 Jan 17;70(2):159–163. doi: 10.1002/(sici)1097-0215(19970117)70:2<159::aid-ijc4>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  71. Thompson H. J., Adlakha H. Dose-responsive induction of mammary gland carcinomas by the intraperitoneal injection of 1-methyl-1-nitrosourea. Cancer Res. 1991 Jul 1;51(13):3411–3415. [PubMed] [Google Scholar]
  72. Thompson H. J., McGinley J. N., Rothhammer K., Singh M. Rapid induction of mammary intraductal proliferations, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea. Carcinogenesis. 1995 Oct;16(10):2407–2411. doi: 10.1093/carcin/16.10.2407. [DOI] [PubMed] [Google Scholar]
  73. Thompson H. J., McGinley J., Rothhammer K., Singh M. Ovarian hormone dependence of pre-malignant and malignant mammary gland lesions induced in pre-pubertal rats by 1-methyl-1-nitrosourea. Carcinogenesis. 1998 Mar;19(3):383–386. doi: 10.1093/carcin/19.3.383. [DOI] [PubMed] [Google Scholar]
  74. Trichopoulos D. Hypothesis: does breast cancer originate in utero? Lancet. 1990 Apr 21;335(8695):939–940. doi: 10.1016/0140-6736(90)91000-z. [DOI] [PubMed] [Google Scholar]
  75. Unger M., Kiaer H., Blichert-Toft M., Olsen J., Clausen J. Organochlorine compounds in human breast fat from deceased with and without breast cancer and in a biopsy material from newly diagnosed patients undergoing breast surgery. Environ Res. 1984 Jun;34(1):24–28. doi: 10.1016/0013-9351(84)90072-0. [DOI] [PubMed] [Google Scholar]
  76. Van den Berg M., Birnbaum L., Bosveld A. T., Brunström B., Cook P., Feeley M., Giesy J. P., Hanberg A., Hasegawa R., Kennedy S. W. Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Environ Health Perspect. 1998 Dec;106(12):775–792. doi: 10.1289/ehp.98106775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Wang W. L., Porter W., Burghardt R., Safe S. H. Mechanism of inhibition of MDA-MB-468 breast cancer cell growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Carcinogenesis. 1997 May;18(5):925–933. doi: 10.1093/carcin/18.5.925. [DOI] [PubMed] [Google Scholar]
  78. Wassermann M., Nogueira D. P., Tomatis L., Mirra A. P., Shibata H., Arie G., Cucos S., Wassermann D. Organochlorine compounds in neoplastic and adjacent apparently normal breast tissue. Bull Environ Contam Toxicol. 1976 Apr;15(4):478–484. doi: 10.1007/BF01685076. [DOI] [PubMed] [Google Scholar]
  79. White T. E., Rucci G., Liu Z., Gasiewicz T. A. Weanling female Sprague-Dawley rats are not sensitive to the antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol Appl Pharmacol. 1995 Aug;133(2):313–320. doi: 10.1006/taap.1995.1156. [DOI] [PubMed] [Google Scholar]
  80. Wohlfahrt J., Mouridsen H., Andersen P. K., Melbye M. Reproductive risk factors for breast cancer by receptor status, histology, laterality and location. Int J Cancer. 1999 Mar 31;81(1):49–55. doi: 10.1002/(sici)1097-0215(19990331)81:1<49::aid-ijc10>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  81. Wolff M. S., Toniolo P. G., Lee E. W., Rivera M., Dubin N. Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst. 1993 Apr 21;85(8):648–652. doi: 10.1093/jnci/85.8.648. [DOI] [PubMed] [Google Scholar]
  82. Wölfle D. Interactions between 2,3,7,8-TCDD and PCBs as tumor promoters: limitations of TEFs. Teratog Carcinog Mutagen. 1997;17(4-5):217–224. doi: 10.1002/(sici)1520-6866(1997)17:4/5<217::aid-tcm4>3.3.co;2-n. [DOI] [PubMed] [Google Scholar]
  83. Zheng T., Holford T. R., Mayne S. T., Tessari J., Ward B., Carter D., Owens P. H., Boyle P., Dubrow R., Archibeque-Engle S. Risk of female breast cancer associated with serum polychlorinated biphenyls and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene. Cancer Epidemiol Biomarkers Prev. 2000 Feb;9(2):167–174. [PubMed] [Google Scholar]
  84. Zheng T., Holford T. R., Mayne S. T., Ward B., Carter D., Owens P. H., Dubrow R., Zahm S. H., Boyle P., Archibeque S. DDE and DDT in breast adipose tissue and risk of female breast cancer. Am J Epidemiol. 1999 Sep 1;150(5):453–458. doi: 10.1093/oxfordjournals.aje.a010033. [DOI] [PubMed] [Google Scholar]
  85. van't Veer P., Lobbezoo I. E., Martín-Moreno J. M., Guallar E., Gómez-Aracena J., Kardinaal A. F., Kohlmeier L., Martin B. C., Strain J. J., Thamm M. DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study. BMJ. 1997 Jul 12;315(7100):81–85. doi: 10.1136/bmj.315.7100.81. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES