Catechol estrogens as biomarkers for mammary gland cancer

Abstract

Abstract. The origin of human tumors has been attributed to the exposure to several environmental chemicals and implicated in the increase of incidence in breast cancer. Progression of breast cancer follows a complex multistep process that seems to depend on various exogenous and endogenous factors. The aim of this study was to examine the effects of the organophosphorous pesticide malathion in the presence of estrogen on neoplastic transformation of rat mammary glands. Virgin female rats were sacrificed after 30, 124 and 240 days of 5-day injections twice a day. There were four groups: i) control, ii) malathion (22 mg/100 g body weight, BW), iii) 17β-estradiol (30 µg/100 g BW) and iv) combination of both. Progressive alterations in ducts were observed by the effect of malathion in comparison to control after 240 days. Ducts markedly increased in size and number of cells per square millimeter and tumors similar to ductal carcinoma were originated. The increase in number of proliferative ducts per square millimeter was significantly (P<0.05) higher in malathion-treated animals compared to the other groups. Progressive alterations in lobules with estrogen treatment were found after 240 days. Lobules became markedly abnormal, referred to as secretory lobules, increased in number and size and the tumors originated were similar to lobular carcinoma. The increase in number of secretory lobules was significantly (P<0.05) higher in estrogentreated animals compared to the other groups. Treatment with the combination of malathion and estrogen gave rise to tumors constituted of both proliferative ducts and secretory lobules as well as formation of estrogen metabolites such as 2 and 4 catechol estrogens in the blood of the animals after 240 days. We concluded that morphological changes and alterations in the blood of the animals can be used as biomarkers for mammary gland cancer.

Malignant Transformation of Rat Kidney Induced by Environmental Substances and Estrogen

“…Other studies showed that 17β-estradiol in combination with pesticides such as parathion and malathion induced malignant lung and mammary cancer transformations in rats [2,4,60] as well as in in vitro studies using the immortalized MCF-10F [61]. Previous in vitro experiments showed that estrogen combined with parathion, another organophosphorous pesticide, altered cell proliferation and induced transformation of the MCF-10F cell line [60].…”

“…The interaction of chemical carcinogens with healthy cells associated with exogenous hormones can induce genomic damage and subsequently cause cancer with the ability of metastasize other tissues [1,2,3,4]. The carcinogenesis process needs several mutational events to produce damage to the genome, and subsequent cell proliferation of these injured cells.…”

State of the evidence 2017: an update on the connection between breast cancer and the environment

“…Dichloro-diphenyl-trichloroethane (DDT) was the first widely used synthetic pesticide. It is credited on the one hand with the eradication of malaria in the United States and Europe and on the other with long-term devastating effects on reproductive success in wildlife and adverse health effects in humans [ 449 ]. Banned in most countries for agricultural use, DDT is still used for malaria control in many countries, especially in sub-Saharan Africa [ 450 ].…”

Carcinogenicity of Malathion and Estrogen in an Experimental Rat Mammary Gland Model

“…Experimental studies have shown that environmental substances (e.g., DDT, polychlorinated biphenyls, 4-nonylphenol,4-octylphenol) seem to be involved in the etiology of breast cancers and can promote mammary cancer [7,8]. Such substances have been associated with the use of organophosphorous insecticides in agriculture and in non-occupational situations as exposure to contaminated clothing, soil, ground and surface water, as well as drifts from aerial spraying of pesticides [9][10][11] and it also has been associated with prolonged exposure to female hormones [12].…”

“…The structure of a normal rat mammary gland is composed of a single primary or main lactiferous duct that branches into alveolar buds (ABs) and secondary ducts that are narrow and straight and end in small clubshaped terminals, called terminal end buds (TEBs) that are equivalent to the terminal ductal lobular unit in the human breast, considered the site of origin of human breast carcinomas [14,15]. The susceptibility of the mammary gland to M alone and in the presence of E was previously analyzed in an established rat mammary gland model already reported [2,12].…”