Long-term carcinogenicity bioassay of the herbicide atrazine in F344 rats

Pintér, A.; Török, György; Börzsöbyi, M.; Surján, A.; Csik, M; Kelecsényi, Zs.; Kocsis, Zs.

doi:10.1016/0165-1161(90)90116-6

Cited by 34 publications

(43 citation statements)

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“…48) However, in other investigations, mammary tumor development was only noted in SD and not F344 rats, and only at or above a threshold dose (the MTD) that interferes with normal estrous cycling, causing prolonged exposure to endogenous estrogen. 16,17) SD rats exhibiting persistent estrus also have a prolonged elevation of estrogen secretion, so it is proposed that the triazine-associated mammary tumor response is promoted by the test animal's own estrogen from ovarian follicles that fail to ovulate.…”

Section: Discussionmentioning

confidence: 99%

Possible enhancing effects of atrazine and nonylphenol on 7,12‐dimethylbenz[a]anthracene‐induced mammary tumor development in human c‐Ha‐ras proto‐oncogene transgenic rats

Fukamachi¹,

Han

Kim

et al. 2004

Cancer Science

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Our transgenic (Tg) strain carrying copies of the human c-Ha-ras proto-oncogene is highly susceptible to 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis, possibly due to activation of the transgene, and can be used in medium-term bioassay models to test for modifying effects of estrogenic environmental compounds on tumor development. The present study was conducted to assess the influence of dietary feeding of the endocrine disruptors atrazine and nonylphenol on DMBA-induced carcinogenesis in c-Ha-ras Tg rats. Animals of both sexes were given a single oral dose of DMBA (25 mg/kg body weight) at 50 days of age and thereafter received soybean-free diet containing 5, 50 or 500 ppm atrazine, or 10, 25, 100 or 250 ppm nonylphenol. In female Tg rats, atrazine at a dose of 5 ppm increased the incidences of mammary adenomas and adenocarcinomas (P < < < <0.01 and P < < < <0.05), while 50 ppm increased the adenocarcinoma incidence (P < < < <0.05). In males, skin tumor development, in contrast, was significantly decreased at the highest dose. Nonylphenol at 10 ppm increased adenocarcinoma and total mammary tumor multiplicity in female Tg rats (P < < < <0.05), but there was no dose dependence, a significant quadratic dose-response trend rather being observed (P < < < <0.05). In vitro, atrazine did not cause proliferation of MCF-7 cells at any of a range of doses tested. These results suggest that endocrine disruptors may enhance mammary carcinogenesis, but only in a certain limited dose range under the present experimental conditions. The doses applied, moreover, were all extremely high compared to the possible environmental human exposure levels. (Cancer Sci 2004; 95: 404-410) t is well documented that estrogen is an obligatory factor for development of the mammary gland.1, 2) The hormone also plays an important role in both the etiology and treatment of mammary cancer and accumulating evidence indicates that slightly elevated levels of circulating estrogens may predispose to tumorigenesis.3, 4) Exogenous estrogens may similarly increase mammary cancer risk.5-7) This may be of considerable importance, since recently, a number of environmental chemicals impacting on the endocrine system (endocrine disruptors) have been shown to exhibit estrogenic activity, these including triazine derivatives and alkylphenolic compounds.Among the symmetrical triazine-type herbicides, atrazine (6-chloro-N 2 -ethyl-N 4 -isopropyl-1,3,5-triazine-2,4-diamine) is one of the most widely and heavily used herbicides all over the world. It is employed in agriculture as a selective pre-and postemergence agent for annual control of grass and broad-leaved weeds. A number of studies have suggested that atrazine is an endocrine disruptor [8][9][10][11][12][13][14][15] and in female Sprague-Dawley, but not other strains of rats, high doses (50-1000 ppm) in the diet have been found to be associated with an increased incidence and/or an earlier onset of mammary gland tumors. [16][17][18][19][20] Alkylphenol polyethoxylates are the se...

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Section: Discussionmentioning

confidence: 99%

Possible enhancing effects of atrazine and nonylphenol on 7,12‐dimethylbenz[a]anthracene‐induced mammary tumor development in human c‐Ha‐ras proto‐oncogene transgenic rats

Fukamachi¹,

Han

Kim

et al. 2004

Cancer Science

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“…This finding, paired with studies showing increased incidence of mammary tumors in rats exposed to chlorotriazines (4,5), prompted action by the EPA. The three chlorotriazines were classified as Group C (possible human) carcinogens.…”

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confidence: 93%

Triazine Herbicide Exposure and Breast Cancer Incidence: An Ecologic Study of Kentucky Counties

Kettles¹,

Browning²,

Prince³

et al. 1997

Environmental Health Perspectives

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“…Atrazine has been reputed to be nong enotoxic (8) , and a role in hormonally mediated tumo rs has been propo sed (7) . Neverth eless, atrazine is muta genic in some experimental sys tems (7) and has been reputed to be genotoxic by the Italian Toxicological Commission (9).…”

Section: 7mentioning

confidence: 99%

“…Our study says nothing about the po ssible role of atrazi ne in other human health outcomes. Atrazine is genotoxic (5,6), causes cancer in anim als (7)(8)(9)(10), and has been linked to ovarian cancer in women ( I I). Gi ven the hormonal acti vities of atrazi ne ( 12,13) , th e highest priority should be given to replicating the ovarian cancer study and evaluating atrazine' s rel ationship with cancers of the breast, endometrium, and prost ate in population s exposed occupationally and populations ex pos ed through contaminated drinking water.…”

Section: Authors' Replymentioning

confidence: 99%

Re: "Role of the herbicide atrazine in the development of non-Hodgkin`s lymphoma" by S Hoar Zahm, DD Weisburger, KP Kantor, FF Holmes, A Blair. Scand J Work Environ Health 1993; 19:108-14.

Crosignani¹,

Berrino²

1994

Scand J Work Environ Health

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Long-term carcinogenicity bioassay of the herbicide atrazine in F344 rats

Cited by 34 publications

References 0 publications

Possible enhancing effects of atrazine and nonylphenol on 7,12‐dimethylbenz[a]anthracene‐induced mammary tumor development in human c‐Ha‐ras proto‐oncogene transgenic rats

Possible enhancing effects of atrazine and nonylphenol on 7,12‐dimethylbenz[a]anthracene‐induced mammary tumor development in human c‐Ha‐ras proto‐oncogene transgenic rats

Triazine Herbicide Exposure and Breast Cancer Incidence: An Ecologic Study of Kentucky Counties

Re: "Role of the herbicide atrazine in the development of non-Hodgkin`s lymphoma" by S Hoar Zahm, DD Weisburger, KP Kantor, FF Holmes, A Blair. Scand J Work Environ Health 1993; 19:108-14.

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