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Biphasic effects of chromium compounds on catecholamine secretion from bovine adrenal medullary cells.

CrO3 was found to affect norepinephrine release in a biphasic manner: at concentrations above 100 microM, it inhibited, while at concentrations below 10 microM, it enhanced DMPP- and high K+-induced [3H]norepinephrine (NE) release from bovine adrenal medullary cells. Similar effects were found for K2Cr2O7. CrO3 inhibited the 45Ca2+ uptake induced by DMPP and high K+, suggesting that the voltage-gated Ca2+ channels are possible sites of the inhibitory action of CrO3. CrCl3, possessing a trivalent state in contrast to the hexavalent states of CrO3, K2Cr2O7, inhibited DMPP-induced [3H] release and inhibited, to a lesser extent, high K+-induced [3H]-NE release, suggesting that nicotinic receptors are also possible sites of Cr3+ action. In medullary cells permeabilized with digitonin, both CrO3 and CrCl3 induced [3H]-NE release from cells preloaded with [3H]-NE. In intact cells, CrO3 but not CrCl3 enhanced secretagogue-induced [3H]-NE release and entered into the cells as demonstrated by fluorescence quenching experiments. These results suggest that chromium compounds can induce catecholamine secretion after entering the cytoplasm. The enhancement of norepinephrine release induced by chromium ions appears to be due to interference with the intracellular functions of Ca2+ in the cytoplasm.

Adrenal Medulla↗

Interactive effect of chromium compounds and a fungal parasite on carp eggs.

A fungal parasite (Saprolegniales) of carp eggs was exposed to hexavalent and trivalent chromium compounds at concentrations identical to those used in a study of the effects of the same compounds on carp eggs hatchability. Comparison of data from both experiments revealed that increased egg mortality and increased fungal growth were cooupled at low concentrations of the compounds. A mechanism for the interaction of a chemical stress and a biological stress on carp egg survival in natural systems is presented.

Animals↗

Cytotoxic and clastogenic effects of soluble chromium compounds on mammalian cell cultures.

The inhibition of cell growth, the reduction of cell survival and the induction of chromosome aberrations and of sister chromatid exchange (SCE) have been determined in cultured hamster cell lines (BHK and CHO) treated with 11 water-soluble compounds of hexavalent and trivalent chromium. All Cr6+ compounds inhibit growth of BHK cells and reduce survival of CHO cells to levels comparable to those obtained only after exposure to 100--1000 times higher Cr3+ concentrations. The cytotoxicity curves obtained with the different Cr6+ compounds are almost overlapping, whereas marked differences of activity are noticeable among Cr3+ compounds. Giant cells are obtained after exposure to Cr6+ and Cr3+ compounds, as shown by the rise of DNA and RNA per cell, and are due to the blockage of the cell cycle without sudden inhibition of macromolecular syntheses. Both Cr6+ and Cr3+ compounds are able to induce chromosome aberrations, whereas Cr3+ is absolutely incapable of inducing SCE, only Cr6+ being active. The frequency of chromosome aberrations is increased about 10-fold after exposure to 1.0 micrograms/ml Cr6+, whereas it is only doubled after treatment with up to 150 micrograms/ml Cr3+. On the other hand, in spite of the sensitivity of CHO cells to the induction of SCE by mitomycin C, the frequency of SCE hardly doubles after exposure to Cr6+ compounds. The present data confirm that Cr6+ compounds are characterized by a marked cytotoxicity and clastogenic action on mammalian cell cultures and show that Cr3+ compounds, though cytotoxic only at extremely high concentrations and not increasing the frequency of SCE, are not completely without cytogenetic effect, as they are able to induce chromosome aberrations.

Animals↗

Welding fumes and chromium compounds in cell transformation assays.

Fumes generated from mild steel and stainless steel welding were collected on paper filters and tested in the BHK and SHE cell transformation assays. Fumes from the manual metal arc welding of stainless steel (MMA/SS) had a toxic and transforming effect attributable to their Cr(VI) content. The fumes from metal inert gas stainless steel (MIG/SS) welding also had a toxic effect but this was 2-3 times greater than that expected from their soluble Cr(VI) content based on the activity of soluble Cr(VI) from pure chromium compounds. When collected in an impinger, the fumes from MIG/SS were found to contain approximately 10 times the soluble Cr(VI) content of samples collected on filters. This additional Cr(VI), when collected in a water impinger, also exhibited a greater toxicity compared with that found for the additional Cr(VI) collected in an impinger filled with growth medium. This comparison implies the presence of a short-lived biologically active Cr(VI) species usually lost in conventional sampling techniques. It also implies that there is a detoxification step associated with the formation of Cr(VI) organic complexes. Relatively insoluble Cr(VI) compounds showed a higher toxic and transforming effect in the BHK assay than could be ascribed to the soluble Cr(VI) content of the medium, indicating the importance of phagocytosis as a pathway for the uptake of Cr(VI) and other toxic substances from particulates.

Animals↗

Increased mutagenicity of chromium compounds by nitrilotriacetic acid.

Nitrilotriacetic acid trisodium salt (NTA), which is a substitute for polyphosphates in household laundry detergents, and N-nitrosoiminodiacetic acid (NIDA), a derivative of NTA produced by metabolism of soil microorganisms, were tested for in vitro mutagenicity in bacteria and yeasts. No gene reversions in five strains of Salmonella typhimurium (TA 1535, TA1537, TA1538, TA98, and TA100), no forward gene mutations in Schizosaccharomyces pombe P1, and no mitotic gene conversions at two loci in Saccharomyces cerevisiae D4 were induced by NTA (up to 870 micrograms/plate or 40 micrograms/ml) and NIDA (up to 2,000 micrograms/plate or 1,000 micrograms/ml), independently of the presence of rat liver metabolic activation. The influence of NTA on the mutagenic and clastogenic activity of several chromium compounds was examined in the Salmonella/microsome assay and in the sister chromatid exchange (SCE) assay in mammalian cell cultures (Chinese hamster ovary [CHO] line). NTA does not affect the genetic inactivity of water-soluble Cr(III) (Cr2[SO4]3) and the direct mutagenicity of soluble Cr(VI) (Na2CrO4,K2Cr2O7) compounds. The very insoluble Cr(VI) compounds PbCrO4 and PbCrO4 X PbO are instead clearly mutagenic in the Salmonella/microsome assay (TA100 strain) only in the presence of NTA or NaOH. The mutagenicity of lead chromates is correlated with the amounts of Cr(VI) solubilized by NTA or alkali, as detected by the colorimetric reaction with diphenylcarbazide and atomic absorption spectrophotometry. In the SCE assay, the insoluble lead chromates are directly clastogenic owing to prolonged treatment conditions and cellular endocytosis. The chromosome-damaging activity of PbCrO4 is significantly increased by NTA but not by NaOH.

Acetates↗

Cytotoxic, mutagenic and clastogenic effects of industrial chromium compounds.

Ten Cr(III) compounds, used in the leather tanning industry, and a Cr(III) compound, containing chromite and used as a pigment, were tested for cytotoxicity (inhibition of growth and survival of cultured hamster cells), mutagenicity (point mutations in S. typhimurium) and clastogenic activity (chromosomal aberrations and sister chromatid exchanges in hamster cells). Reference Cr compounds were potassium dichromate as Cr(VI), and chromium chloride and two different preparations of chromium nitrate as Cr(III). A contamination with Cr(VI) was detected in some of the Cr(III) tannins, chromite and one chromium nitrate. Cr(III) compounds were cytotoxic at concentrations of Cr(III) 100-500 times higher than Cr(VI), but contaminated Cr(III) compounds showed a significant cytotoxicity. Reference Cr(VI) but not Cr(III) was mutagenic: of the contaminated compounds only chromite and chromium nitrate, which contained higher levels of Cr(VI), were found to be mutagenic. The frequency of sister chromatid exchanges was significantly increased only by Cr(VI) and the more contaminated Cr(III) compounds. However, an increase of chromosomal aberrations was produced also by reference Cr(III) salts and the weakly contaminated industrial Cr(III) compounds. These results confirm the view that the active mutagenic agent in intact cell systems is Cr(VI), but indicate that industrial Cr(III) compounds cannot be considered genetically inert, as they can be contaminated by Cr(VI) and induce chromosomal aberrations.

Animals↗

Sister-chromatid exchanges induced by some chromium compounds in human lymphocytes in vitro.

Treatments with various concentrations of K2Cr2O7, CaCrO4 and CrO3 were given to human lymphocytes cultured in presence of BrdUrd for 2 replicative cycles. Sister-chromatid exchanges (SCEs) were visualized by a combination of fluorescent and Giemsa techniques. In all cases, the higher the concentrations the higher the frequencies of SCEs per metaphase and per chromosome. On a concentration basis, the order of effectiveness in producing SCEs was: CaCrO4 much greater than CrO3 greater than K2Cr2O7.

Bromodeoxyuridine↗

Effect of long-term ingestion of chromium compounds on aggression, sex behavior and fertility in adult male rat.

The effects of long-term ingestion of chromium chloride (trivalent compound) and potassium dichromate (hexavalent compound) was investigated on sexual behavior, aggressive behavior and fertility in male rats. Adult male rats were exposed to chromium chloride and potassium dichromate in drinking water at a concentration of 1000 ppm for 12 weeks. The exposure of male rats to chromium chloride and potassium dichromate reduced the number of mounts. The exposure of male rats to potassium dichromate increased the time to ejaculation. On the other hand, the exposure of male rats to chromium chloride and potassium dichromate increased the post ejaculatory interval. The number of animals ejaculating were reduced in chromium chloride and potassium dichromate exposed male rats. The exposure of male rats to chromium chloride and potassium dichromate decreased lateralizations, boxing bouts and fights with stud male. The exposure of male rats to chromium chloride and potassium dichromate had no effect on fertility. Testes, seminal vesicle and preputial gland weights were significantly reduced in chromium chloride- and potassium dichromate-exposed males. In conclusion, the long-term ingestion of chromium chloride and potassium dichromate would have adverse effects on sexual behavior and territorial aggression in adult male rat.

Animals↗

Sister chromatid exchange induced by chromium compounds in human lymphocytes.

The objective of this study was to study was to compare chromium (Cr), nickel-chromium (Ni-Cr), and control groups for sister chromatid exchange (SCE) in lymphocytes to obtain an understanding of the mutagenic effect of Cr(VI) in humans. Subjects totaled 91 persons from the 3 groups, including 14 Cr and 34 Ni-Cr electroplating workers and 43 control group members. Results showed that blood and urine Cr concentrations were highest among Cr workers (11.39 microg/l, 14.7 microg/g creatinine), next highest among Ni-Cr workers (5.28 microg/l, 6.2 microg/g creatinine), and lowest among the control group (2.36 microg/l, NA). After adjustment for smoking habits, SCE/cell values were 10.6, 9.4, and 8.3 for Cr workers, Ni-Cr workers, and controls, respectively. A synergetic effect was shown on HFC (high-frequency cells) percentages for Cr workers who also smoked. Odds ratios were 31.78 and 3.66 that Cr and Ni-Cr workers would have higher HFC percentages than the control group, respectively. The authors conclude that SCE in lymphocytes is useful for evaluation of the biological effects of environmental mutagens.

Adult↗