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Abstract

Lung cancers are significantly increased among workers exposed to chromate (Cr6+, Cr3+), chromium pigments (Cr6+) and chromium plating (Cr6+). Chromium lung burdens and cancer risk increase proportionately with duration of employment at long latencies. However, this epidemiologic information alone is insufficient in determining whether Cr6+ or Cr3+ are equally important in causing cancer. We have attempted to combine epidemiologic data with data from the Drosophila melanogaster somatic-mutation-recombination-test and from the in vitro electron-spin-resonance spectroscopy study to demonstrate that following somatic recombination plays a more important role than somatic mutation in chromium carcinogenesis. Cr4+ is more important than Cr5+ or Cr6+ in inducing somatic recombination while Cr6+ produces more and bigger clones than Cr4+ in somatic mutation. Cr3+ produces negative results in this fruit-fly wing-spot-assay. When the larvae and flies exposed to Cr6+ and Cr4+ are examined by ESR, only Cr5+ and Cr3+ are found. Thermodynamic parameters deltaE, deltaH, and deltaS are also estimated from these latter experiments to explain the relative importance of Cr6+, Cr4+, Cr3+ in chromium carcinogenesis among exposed industrial workers.

Nutritional supplement chromium picolinate causes sterility and lethal mutations inDrosophilamelanogaster

“…Epidemiologic analysis of humans exposed to chromate and studies in animal and cell culture models demonstrate that exposure to chromium compounds is strongly correlated with DNA damage in somatic cells and to elevation of cancer rates in humans (31). These studies indicate that Cr are particularly strong in inducing genotoxic effects, whereas trivalent chromium appears to be substantially more innocuous.…”

“…These studies are of substantial concern given the popularity of [Cr(pic) 3 The wing spot test of Drosophila has become an efficient and sensitive means of detecting damage to DNA in somatic cells. In this test, larvae are fed an agent to be tested for periods ranging from 2 days to a few hours, and effects on DNA are then monitored in adults (30)(31)(32)(33)(34). During the larval phase of the life cycle, the imaginal disks, the precursors to adult structures that develop during the pupal stage, are undergoing active mitosis.…”

“…Such assays have been performed for numerous chromium complexes, and the results of such analyses strongly parallel those of studies in mammalian cells. These studies show that hexavalent and tetravalent chromium species exhibit high levels of recombinogenic activity, whereas the trivalent CrCl 3 is inactive (30)(31)(32)(33)(34). None of these studies, however, address the effect of [Cr(pic) 3 ] on dividing somatic cells.…”

“…Exposure to an agent is shortterm, and effects are restricted solely to mitotic cells (where the damage induced by chromium compounds is caused by chromosome breakage and subsequent recombination and point mutations; ref. 31). In this study, in light of concerns over the effects of long-term supplementation and possible effects in subsequent generations, we used a somewhat different approach that allows the assessment of the effects of exposure to juveniles on developmental processes and to possible mutagenic activity in the germ line.…”

Review of Chromium (VI) Apoptosis, Cell-Cycle-Arrest, and Carcinogenesis

“…Katz et al (89) and Chiu et al (90) further evaluated Cr(VI), Cr(IV) and Cr(III) for genotoxic effects in somatic tissue of D. melanogaster with SMART wing spot test. The results suggest both Cr(VI) and Cr(VI) are highly genotoxic in flies via induction of mitotic recombination.…”