, 1996). The MT-3 isoform is also expressed in the proximal tubules and other tubular elements of the human kidney (Garrett et al., 1999). The cortex of the human kidney has been shown to accumulate cadmium, as a function of age, in humans without occupational exposure (Satarug et al., 2002 and Satarug et al., 2010). Accumulation is assumed to occur through cadmium’s interaction with MT and accumulation has been shown to reach a plateau at approximately 50 years

Pirfenidone manufacturer of age. Despite the MT’s being looked upon as having a protective role against heavy metal toxicity in general, and the proximal tubule in particular (Liu et al., 1995, Liu et al., 1998, Liu et al., 2000 and Masters et al., 1994), the fact remains Selleck Ku 0059436 that the kidney and the proximal tubule is the cell type critically affected by chronic exposure to cadmium (Andrews, 2000, Bernard et al., 1976, Bosco et al., 1986 and Gonich et al., 1980). It has been shown in human population studies that even low exposure to cadmium alters renal tubule function (Akesson et al., 2005). Thus, there is evidence in the kidney that pre-existing expression of MT in the renal tubules both protects the kidney from cadmium exposure, but

this expression might also render the organ susceptible to the chronic effects of the metal. There is little evidence, either for or against, that would support a similar role for MT-3 expression in human skin as regards the chronic effects of exposure to arsenic. The present study demonstrates

that MT-3 is prominently expressed in the majority of cells comprising the nevus, dysplastic nevus, in situ melanoma, superficial melanoma, and deeply invasive melanoma. Although the sample set was relatively Rucaparib chemical structure small, there was no indication that expression was variable within or between disease categories. A consequence of this pattern of constant MT-3 expression is that the melanocytes, in all stages of progression, are able to continue to bind and accumulate As+3 in an environment where exposure to As+3 is at elevated levels. Unfortunately, there is very little information in the literature on conditions or mechanisms in vivo that would influence the release of As+3 from MT-3 inside a cell or tissue. One could speculate that if ultraviolet radiation influenced the release of As+3 from MT-3, it might impact on emerging research which suggests a linkage between the development of melanoma and co-exposure to As+3 and ultraviolet radiation ( Cooper et al., 2014). The expression of MT-1 and -2 has been examined in patients with melanoma. It was shown that a gain of expression of MT-1 and -2 is an adverse prognostic and survival factor for patients with this cancer ( Weinlick et al., 2003 and Weinlick et al., 2006). In contrast to MT-3, MT-1 and -2 is not expressed in the nevus and is gained later during the development of the cancer.