The cytotoxicity and genotoxicity of hexavalent chromium in Steller sea lion lung fibroblasts compared to human lung fibroblasts.

In this study we directly compared soluble and particulate chromate cytotoxicity and genotoxicity in human (Homo sapiens) and sea lion (Eumetopias jubatus) lung fibroblasts. Our results show that hexavalent chromium induces increased cell death and chromosome damage in both human and sea lion cells with increasing intracellular chromium ion levels. The data further indicate that both sodium chromate and lead chromate are less cytotoxic and genotoxic to sea lion cells than human cells, based on an administered dose. Differences in chromium ion uptake explained some but not all of the reduced amounts of sodium chromate-induced cell death. By contrast, uptake differences could explain the differences in sodium chromate-induced chromosome damage and particulate chromate-induced toxicity. Altogether they indicate that while hexavalent chromium induces similar toxic effects in sea lion and human cells, there are different mechanisms underlying the toxic outcomes.

Cytotoxicity and genotoxicity of hexavalent chromium in human and North Atlantic right whale (Eubalaena glacialis) lung cells.

Humans and cetaceans are exposed to a wide range of contaminants. In this study, we compared the cytotoxic and genotoxic effects of a metal pollutant, hexavalent chromium [Cr(VI)], which has been shown to cause damage in lung cells from both humans and North Atlantic right whales. Our results show that Cr induces increased cell death and chromosome damage in lung cells from both species with increasing intracellular Cr ion levels. Soluble Cr(VI) induced less of a cytotoxic and genotoxic effect based on administered dose in right whale (Eubalaena glacialis) cells than in human (Homo sapiens) cells. Whereas, particulate Cr(VI) induced a similar cytotoxic effect but less of a genotoxic effect based on administered dose in right whale cells than in human cells. Differences in chromium ion uptake explained soluble chromate-induced cell death but not all of the soluble chromate-induced chromosome damage. Uptake differences of lead ions could explain the differences in particulate chromate-induced toxicity. The data show that both forms of Cr(VI) are less genotoxic to right whale than human lung cells, and that soluble Cr(VI) induces a similar cytotoxic effect in both right whale and human cells, while particulate Cr(VI) is more cytotoxic to right whale lung cells.

Particulate hexavalent chromium is cytotoxic and genotoxic to the North Atlantic right whale (Eubalaena glacialis) lung and skin fibroblasts.

Hexavalent chromium compounds are present in the atmosphere and oceans and are established mutagens and carcinogens in human and terrestrial mammals. However, the adverse effects of these toxicants in marine mammals are uncertain. Previously, we reported that North Atlantic right whales, one of the most endangered great whales, have tissue chromium levels that are high, levels that may pose a risk to the whale's health. Furthermore, the study suggested that inhalation may be an important exposure route. Exposure to chromium through inhalation is mainly because of particulate compounds. However, the toxicity of particulate chromium compounds in marine mammal cells is unknown. Accordingly, in this study, we tested the cytotoxic and genotoxic effects of particulate hexavalent chromium in primary cultured lung and skin fibroblasts from the endangered North Atlantic right whale. Cytotoxicity was measured by clonogenic survival assay, and genotoxicity was measured as production of chromosome aberrations. Particulate hexavalent chromium induced cytotoxicity and genotoxicity in a concentration-dependent manner in both right whale lung and skin fibroblasts. Lung fibroblasts were more resistant to chromium cytotoxicity, but presented with more chromosome damage than skin fibroblasts. These data further support the hypothesis that chromium may be a health concern for the endangered North Atlantic right whale.

Particulate and soluble hexavalent chromium are cytotoxic and genotoxic to Steller sea lion lung cells.

Hexavalent chromium is an environmental contaminant. Within the environment, marine waters are a common site for hexavalent chromium deposition. We have recently reported significantly high levels of chromium in skin tissue from North Atlantic right whales. These findings demonstrate that marine species are being exposed to chromium. It is possible that such exposures may be playing a role in population declines evident among certain marine mammals, such as the Steller sea lion. We developed a Steller sea lion lung cell line from Steller sea lion lung tissue. Hexavalent chromium was cytotoxic to these primary lung fibroblasts as 1, 2.5, 5, 10 and 25microM sodium chromate induced 104, 99, 92, 58 and 11% relative survival, respectively. It was also genotoxic as 0, 1, 2.5, 5 and 10microM sodium chromate damaged chromosomes in 6, 11, 21, 36, and 39% of metaphases and damaged 6, 12, 27, 49 and 57 total aberrations in 100 metaphases, respectively. We also considered the toxicity of particulate hexavalent chromium, as it is the more potent carcinogen in humans. We found that 0.1, 0.5, 1, 5 and 10microg/cm(2) particulate chromate induced 95, 88, 91, 70, and 52% relative cell survival, respectively. These concentrations were genotoxic and damaged chromosomes in 9, 13, 18, and 23% of metaphases and induced 9, 15, 20 and 30 total aberrations per 100 metaphases, respectively. These data indicate that if sufficiently exposed, chromium may adversely affect the struggling Steller sea lion population. It would be prudent to investigate the effects chromium has in other Steller sea lion organs in order to derive a better understanding of how chromium in the marine environment may be affecting the declining Steller sea lion population.

Medaka (Oryzias latipes) as a sentinel species for aquatic animals: Medaka cells exhibit a similar genotoxic response as North Atlantic right whale cells.

Hexavalent chromium (Cr(VI)) is emerging as a major concern for aquatic environments, particularly marine environments. Medaka (Oryzias latipes) has been used as a model species for human and aquatic health, including the marine environment, though few studies have directly compared toxicological responses in medaka to humans or other aquatic species. We used a medaka fin cell line to compare the genotoxic response of medaka to Cr(VI) to the response observed in North Atlantic right whale cells to see if responses in medaka were similar to those of other aquatic species, particularly aquatic mammals. We used the production of chromosomal aberrations as a measure of genotoxicity. We found that in medaka cells, concentrations of 1, 5 and 10 microM sodium chromate damaged 17, 32 and 43% of metaphases, respectively and these same concentrations 1, 2.5, 5 and 10 microM sodium chromate damaged 14, 24 and 49% of metaphases, respectively, in North Atlantic right whale lung cells and 11, 32 and 41% of metaphases, respectively, in North Atlantic right whale testes cells. These data show that genotoxic responses in medaka are comparable to those seen in North Atlantic right whale cells, consistent with the hypothesis that medaka are a useful model for other aquatic species.

Hexavalent chromium is cytotoxic and genotoxic to the North Atlantic right whale (Eubalaena glacialis) lung and testes fibroblasts.

Although hexavalent chromium is a known genotoxic agent in human and terrestrial mammals and is present in seawater and air, its effects on marine mammals including the endangered North Atlantic right whale are unknown and untested. The present study investigated the cytotoxic and genotoxic effects of hexavalent chromium in primary cultured North Atlantic right whale lung and testes fibroblasts and levels of total chromium in skin biopsies from North Atlantic right whales. Cytotoxicity was measured by clonogenic survival assay. Genotoxicity was measured as production of chromosome aberrations. Tissue chromium levels were determined from skin biopsies of healthy free-ranging whales in the Bay of Fundy using inductively coupled plasma optical emission spectroscopy. Hexavalent chromium-induced concentration-dependent increases in right whale lung and testes fibroblast cytotoxicity with the testes more sensitive to the cytotoxic effects. It also induced concentration-dependent increases in chromosomal aberrations in both cell types with no significant difference in sensitivity. Skin biopsy data indicate that North Atlantic right whales are exposed to chromium and accumulate a range of 4.9-10 microg Cr/g tissue with a mean of 7.1 microg/g. Hexavalent chromium is cytotoxic and genotoxic to North Atlantic right whale cells. The whales have tissue chromium levels that are concerning. These data support a hypothesis that chromium may be a concern for the health of the North Atlantic right whales. Considering these data with chromium chemistry, whale physiology and atmospheric chromium levels further suggest that inhalation may be an important exposure route.