%0 Journal Article
%T The Mammary Gland Carcinogens: The Role of Metal Compounds and Organic Solvents
%A Stephen Juma Mulware
%J International Journal of Breast Cancer
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/640851
%X The increased rate of breast cancer incidences especially among postmenopausal women has been reported in recent decades. Despite the fact that women who inherited mutations in the BRCA1 and BRCA2 genes have a high risk of developing breast cancer, studies have also shown that significant exposure to certain metal compounds and organic solvents also increases the risks of mammary gland carcinogenesis. While physiological properties govern the uptake, intracellular distribution, and binding of metal compounds, their interaction with proteins seems to be the most relevant process for metal carcinogenicity than biding to DNA. The four most predominant mechanisms for metal carcinogenicity include (1) interference with cellular redox regulation and induction of oxidative stress, (2) inhibition of major DNA repair, (3) deregulation of cell proliferation, and (4) epigenetic inactivation of genes by DNA hypermethylation. On the other hand, most organic solvents are highly lipophilic and are biotransformed mainly in the liver and the kidney through a series of oxidative and reductive reactions, some of which result in bioactivation. The breast physiology, notably the parenchyma, is embedded in a fat depot capable of storing lipophilic xenobiotics. This paper reviews the role of metal compounds and organic solvents in breast cancer development. 1. Introduction Breast cancer accounts for 16% of all cancer deaths among women globally, according to the report by the World Health Organization [1]. It is the most common solid tumor diagnosed in women [2] and there is also an increasing trend in men. Even though some women are genetically predisposed by inheriting the BRCA1 and BRCA2 genes, studies show that an elevated lifetime of estrogen exposure is also another risk factor for breast cancer [3]. The ability of estrogen and estrogen metabolites to generate oxygen reaction species (ROS) which can induce DNA synthesis, increase phosphorylation of protein kinases, and activate transcription factors like AP-1, NRF1, E2F, and CREB which are found to be responsive to oxidants (including solvent toxins and metal compounds) embodies the basis of carcinogenesis by estrogen [4]. Whereas the activation of transcription factors plays a vital role in cell transformation, cell cycle, migration, and invasion, and it increases the genetic instability [5]. Occupational and environmental exposure to metal compounds and organic solvents have contributed to increasing breast cancer cases in the recent decades especially as many women have entered work places since 1960s [6]. It has
%U http://www.hindawi.com/journals/ijbc/2013/640851/