The role of metals in carcinogenesis: biochemistry and metabolism.

Abstract

The oxyanions of vanadium, chromium, molybdenum, arsenic, and selenium are stable forms of these elements in high oxidation states which cross cell membranes using the normal phosphate and/or sulfate transport systems of the cell. Once inside the cell, these oxyanions may sulfuryl transfer reactions. Often the oxyanions serve as alternate enzyme substrates but form ester products which are hydrolytically unstable compared with the sulfate and phosphate esters and, therefore, decompose readily in aqueous solution. Arsenite and selenite are capable of reacting with sulfhydryl groups in proteins. Some cells are able to metabolize redox active oxyanions to forms of the elements in other stable oxidation states. Specific enzymes may be involved in the metabolic processes. The metabolites of these elements may form complexes with small molecules, proteins and nucleic acids which inhibit their ability to function properly. The divalent ions of beryllium, manganese, cobalt, nickel, cadmium, mercury, and lead are stable forms of these elements which may mimic essential divalent ions such as magnesium, calcium, iron, copper, or zinc. These ions may complex small molecules, enzymes, and nucleic acids in such a way that the normal activity of these species is altered. Free radicals may be produced in the presence of these metal ions which damage critical cellular molecules.

Effects of tri-valent (Cr(III)) and hexa-valent (Cr(VI)) chromium on the growth of activated sludge

“…25 mg l −1 of Cr(VI)) had either stimulating [4] or inert [22] effects on biomass growth, a wide range of concentrations have been employed, in order to also identify the lethal doses. It should be pointed out that the actual concentration of Cr species in the growth medium during the experiments may be somehow different than the calculated concentrations, due to the following reasons: (i) due to accumulation of Cr in biomass [23,24] and (ii) due to the biotransformation of Cr(VI) into Cr(III) [15][16][17][18]. This work aims to investigate the growth pattern of activated sludge growing in a rich medium at the presence of calculated quantities of Cr(VI) or Cr(III), and not to investigate the fate of Cr species in the microbial culture.…”

“…Hexa-valent chromium is regarded as more toxic. Indeed, the tri-valent chromium tends to accumulate in the cell membrane, whilst the hexa-valent chromium is capable of penetrating the membrane into the cytoplasm, where it is reduced to tri-valent chromium and reacts with the intracellular material [15][16][17][18].…”

Genetic damage induced by lead chloride in different tissues of fresh water climbing perch Anabas testudineus (Bloch)

“…Inorganic and organic lead enters the environment in several ways (Godwin 2001) and can have diverse effects on organisms, including mimicking essential elements (e.g. calcium, magnesium, iron and zinc) with consequent effects on enzymes containing SH groups (Jennette 1981), increased incorporation of erroneous nucleotides (Johnson 1998) and effects on repair mechanisms in which lead has been implicated as a co-carcinogen (Frascasso et al 2002).…”

Cancer risk from inorganics

“…On the other hand, trivalcnt chromium compounds induce DNA damage in isolated nuclei, purified DNA, or in intact cells if entry is made possible by suitable ligands or endocytosis [188]. Rat liver cclls and microsomal preparations can reduce Cr (VI) to Cr (I11) through the P-450 systcm (reviewed by Babich et al [146]), suggesting that this step is a prerequisite for interaction of chromium with DNA [189]. Rafetto et al [165], and de Flora et aL [188], however, provide evidence that Cr (VI) and Cr (III) both interact with DNA in bacteria but by different mechanisms, i.e., by unbalancing nucleotide pools, and by cross-linking activities, respcctively [188].…”