DDT acceleration of mammary gland tumors induced in the male Sprague-Dawley rat by 2-acetamidophenanthrene

103

We investigated mammary gland diferentiation and cela profationin rsafter exposure 'to, men (2). A recent analysis of chemical plant workers found a more than twofold increase in breast cancer in female workers exposed to dioxin (3), although other studies report negative associations of polychlorinated biphenyls and dioxin with breast cancer (4,5). In one report DDT was associated with a higher risk of developing breast cancer (6), although another study failed to observe a higher risk after DDT exposure (7). DDT, dioxins, polychlorinated biphenyls, and a number of other organochlorine pesticides have been found in breast milk and human adipose tissue (8). Some (200 p1/rat), on days 25, 27, 29, and 31 postpartum. The doses were derived from the literature which showed these chemicals caused alterations to the endocrine system, reproductive tract, or the liver, or from our unpublished data. We killed the rats 18 hr after the last treatment and removed both abdominal glands-one for preparation of a whole mount and the other for processing as a tissue block for sectioning.The whole mount was spread on a slide, fixed in 10% neutral buffered formalin (8-24 hr), defatted in acetone (8-24 hr), rehydrated in 70% ethanol (30 min), rinsed in water (15 min), and stained in alum carmine (2 g/L) overnight. The stained gland was progressively dehydrated in ethanol from 35% to 95% in four steps (30 min/step), then left in 100% ethanol overnight. The glands were subsequently transferred to xylene for clearing for 24 hr, compressed with a second glass slide held with paper clips for 24 hr, and then released and allowed to expand for 6-24 hr before coverslipping using Permount (Fisher Scientific, Atlanta, Georgia).We examined coded whole mounts under light microscopy at 40x and 100x magnification and scored them for the numbers of terminal end buds, terminal ducts, alveolar buds, and lobules. In our evaluations, terminal ductal structures with diameters .100 pm were called terminal end buds, while those of < 100 pm in diameter were called terminal ducts. Terminal ductal structures composed of 5-10 alveoli were called type I lobules. The criteria for identification of the structures were based on the work by Russo and Russo (13). We evaluated the outer portion of the entire gland (periphery to 1.78 mm inward).We measured cell proliferation in the contralateral gland using proliferating cell nuclear antigen (PCNA) as a marker of mitotic activity (20). Formalin-fixed glands were processed for paraffin embedding within 24 hr of their removal from the animal. We cut 5-pm sections and mounted them on Superfrost Plus Electrostatic Slides (Fisher Scientific, Atlanta, Georgia). The sections were deparaffinized and subjected to 3% hydrogen peroxide to quench

Section: Cell Proliferationsupporting

confidence: 84%

Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat.

Brown

Lamartiniere

1995

103

“…(61), exerted a uterotropic effect (62), inhibited the binding in vitro of [ 3 H]-estradiol to the cytosolic estrogen receptor in utero (63), and accelerated mammary gland carcinogenesis induced by 2-acetylamidophenanthrene (64). In mice, the uterotropic effect of DDT increased the weight of the uterus and the development of pseudoestrus (65).…”

Section: Ddt As An Endocrine Disruptormentioning

confidence: 99%

Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks.

Turusov

Rakitsky²,

Tomatis³

2002

539

232

Due to uncontrolled use for several decades, dichlorodiphenyltrichloroethane (DDT), probably the best known and most useful insecticide in the world, has damaged wildlife and might have negative effects on human health. This review gives a brief history of the use of DDT in various countries and presents the results of epidemiologic and experimental studies of carcinogenesis. Even though its use has been prohibited in most countries for ecologic considerations, mainly because of its negative impact on wildlife, it is still used in some developing countries for essential public health purposes, and it is still produced for export in at least three countries. Due to its stability and its capacity to accumulate in adipose tissue, it is found in human tissues, and there is now not a single living organism on the planet that does not contain DDT. The possible contribution of DDT to increasing the risks for cancers at various sites and its possible role as an endocrine disruptor deserve further investigation. Although there is convincing experimental evidence for the carcinogenicity of DDT and of its main metabolites DDE and DDD, epidemiologic studies have provided contrasting or inconclusive, although prevailingly negative, results. The presence and persistence of DDT and its metabolites worldwide are still problems of great relevance to public health. Efficient pesticides that do not have the negative properties of DDT, together with the development of alternative methods to fight malaria, should be sought with the goal of completely banning DDT.

“…An essential characteristic of the model for mammary tumorigenesis (Figure 2) is that the time at which exposures occur is (26), induce tumor-cell proliferation (27), and promote mammary tumor formation in rodents (28,29). The hallmark of estrogen response in the rodent is increased uterine weight, an effect observed with a wide range of environmental agents (Table 4).…”

Section: Timing Of Exposuresmentioning

confidence: 99%

Breast cancer risk and environmental exposures.

Wolff

Weston

1997

Although environmental contaminants have potential to affect breast cancer risk, explicit environmental links to this disease are limited. The most well-defined environmental risk factors are radiation exposure and alcohol ingestion. Diet is clearly related to the increased incidence of breast cancer in developed countries, but its precise role is not yet established. Recent studies have implicated exposure to organochlorines including DDT as a risk factor for breast cancer in the United States, Finland, Mexico, and Canada. Other investigations have discovered associations between breast cancer risk and exposures to chemical emissions and some occupational exposures. Several points must be considered in evaluating the relationship of environmental exposure to breast cancer. Among these considerations are the mechanism of tumorigenesis, timing of environmental exposure, and genetic modulation of exposure. Epidemiologic and ecologic investigations must take into account the very complex etiology of breast cancer and the knowledge that tumorigenesis can arise from different mechanisms. Thus crucial exposures as well as reproductive events related to breast cancer may occur years before a tumor is evident. Moreover, environmental contaminants may alter reproductive development, directly or indirectly, and thereby effect the course of tumorigenesis. Such alterations include change in gender, change in onset of puberty, and inhibition or promotion of tumor formation. Timing of exposure is therefore important with respect to mechanism and susceptibility. Finally, genetic polymorphisms exist in genes that govern capacity to metabolize environmental contaminants. Higher risk may occur among persons whose enzymes either are more active in the production of procarcinogens or fail to detoxify carcinogenic intermediates formed from chemicals in the environment.