Prenatal TCDD and predisposition to mammary cancer in the rat

Brown, Nesbitt D.

doi:10.1093/carcin/19.9.1623

Cited by 135 publications

(114 citation statements)

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“…In our study, most of the palpable tumors were from the abdominal-inguinal glands. In other studies in which tumors were initiated with DMBA (68) or MNU (86,104) at day 50 of age, tumors were located mostly in the thoracic region. Asynchronous postnatal development of the cervical-thoracic versus abdominal-inguinal glands was suggested to explain the predominance of thoracic tumors (88).…”

Section: Discussionmentioning

confidence: 89%

“…However, the increased median number of mammary lesions induced by MNU-TCDD and MNU-1,000× (Table 2) and the increased percentage of rats that developed palpable mammary tumors in the MNU-TCDD group (Figure 4) suggest that these treatments favored the initiation and/or promotion phases of the carcinogenic process. Others found that the carcinogenic potential of chemical initiators (DMBA or MNU) is increased by the administration of TCDD in utero (68), or at relatively low doses of PCB #77 (64), compared to high [PCB #77 (65); TCDD (66)] or repetitive doses (67) of Ah-R agonists, which reduced tumor development. Brown et al (68) suggested that TCDD treatment in utero potentiates the carcinogenic effects of DMBA by increasing the number of terminal end buds (TEBs) at the time of the DMBA injection at 50 days of age; the TEBs are suggested to be the target sites for the carcinogenic effects of chemical initiators (102).…”

Section: Discussionmentioning

confidence: 99%

“…3,3´,4,4´-tetrachlorobiphenyl (PCB #77) can either potentiate the carcinogenic effect of DMBA (64) or prevent further development of mammary tumors in the rat (65). Acute exposure to TCDD (66) or other arylhydrocarbon receptor (Ah-R) agonists (67) in postpubertal rats inhibited mammary tumor development; however, development of the tumors was promoted when TCDD was administered in utero (68).…”

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confidence: 99%

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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.

Desaulniers

Leingartner

Russo

et al. 2001

Environ Health Perspect

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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.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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.

Desaulniers

Leingartner

Russo

et al. 2001

Environ Health Perspect

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“…Also, TCDD or 3,3',4,4'-Tetrachlorobiphenyl (PCB77) administrated to adult rats having DMBA-induced mammary tumors has been reported to inhibit the growth of these tumors 12,13 . Meanwhile, rats treated in-utero with TCDD and then with DMBA at day 50 post partus developed more mammary carcinoma compared to the vehicle-group 10 . Moreover, when PCB77 was coadministrated with DMBA to adult rats, increased mammary carcinoma formation is reported 11 .…”

Section: Introductionmentioning

confidence: 90%

“…There have been limited experiments reported to determine whether dioxins could influence development of chemical-induced mammary carcinogenesis [9][10][11][12][13] . One well established model for the study of mammary carcinogenesis i n v o l v e s t h e u s e o f a s i n g l e o r a l d o s e o f 7 ,1 2 -dimethybenz(a)anthracene (DMBA) to initiate rats mammary carcinoma 14 , where interacting agents can be investigated for their ability to modulate growth of the tumors 15 .…”

Section: Introductionmentioning

confidence: 99%

In-Utero and Lactational Exposure of 3,3',4,4',5-Pentachlorobiphenyl Modulate Dimethlbenz[a]anthracene-Induced Rat Mammary Carcinogenesis.

et al. 2001

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While polychlorinated biphenyls (PCB) are fat-soluble environmental pollutants stored breast fatty tissue and secreted in milk; the precise evidence of breast carcinoma from exposure to PCBs remains unclear. The aim of this study was to investigate the dose-response relationship in-utero and lactational exposure of PCBs congener for dimethlbenz [a]anthracene (DMBA)-induced rat mammary carcinogenesis. Female SD rats were injected (i.g.) with 25 pg, 2.5 ng, 250 ng, 7.5 µg of 3,3',4,4',5-pentachlorobiphenyl (PCB126)/kg, or the vehicle, on days 13 to 19 postconception. Fifty-day-old female offspring were injected (i.g.) with 20 mg DMBA. The concentration of PCB in the liver of the 50-day-old was compared to the vehicle-group, found to be 530-fold higher in the 7.5 µg-group, nearly 21-fold higher in the 250 ng-group, nearly 2.4-fold in the 2.5 ng-group, and nearly 1.2-fold in the 25 pg-group. The expression of CYP1A1 in the liver of the 50-day-old was intensive in the 7.5 µg-and 250 ng-groups, and slight in the 2.5 ng-group, and not observed in the other groups. The observation was terminated when the pups were 170-day-old or the tumor size reached 20mm in diameter. The 7.5 µg-group showed a reduction of mammary carcinogenesis, but the 250 ng-and 2.5 ng-groups revealed increases incidence of carcinoma, while the 25 pg-group showed a similar incidence of the vehicle-group. The time course of tumor development of the 7.5 µg-group was significantly lower than that of the other groups, but that of the 250 ng-group was significantly higher, and that of the 2.5 ng-and 25 pg-groups was similar to that of the vehicle-group. Moreover, the tumors of the 250 ng-group showed the highest cell proliferation, anuploid tumor index, and nuclear grade when compared to those of the other groups. The present studies indicate that in-utero and lactational exposure of relatively low dose PCB acts as an enhancing agent toward DMBA-induced rat mammary carcinogenesis, but that of high dose PCB acts as an inhibiting agent. This effect partly may be due to the in vivo difference at the day of DMBA exposure (50-day-old); between the concentration of PCB and the expression of phase I drug-metabolize enzymes (CYP1A1) converting DMBA into the ultimate carcinogen. (J Toxicol Pathol 2001; 14: 213-224)

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The E3 Ubiquitin Ligase Activity of Transcription Factor AHR Permits Nongenomic Regulation of Biological Pathways

Ohtake

Kato

2011

The AH Receptor in Biology and Toxicology

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Prenatal TCDD and predisposition to mammary cancer in the rat

Cited by 135 publications

References 33 publications

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.

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.

In-Utero and Lactational Exposure of 3,3',4,4',5-Pentachlorobiphenyl Modulate Dimethlbenz[a]anthracene-Induced Rat Mammary Carcinogenesis.

The E3 Ubiquitin Ligase Activity of Transcription Factor AHR Permits Nongenomic Regulation of Biological Pathways

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