Chromosomal effects of heavy metals (Cd, Cr, Hg, Ni and Pb) on cultured mammalian cells in the presence of nitrilotriacetic acid (NTA)^†

Interactions of chromium with nitrilotriacetic acid (NTA) in the induction of genetic effects in bacteria†

“…14 NTA also elicits the ability of PbCrO 4 to induce micronuclei and chromosomal aberrations in human lymphocytes 16 as well as DNA damage in E. coli (present results). Induction of SCE in cultured mammalian cells and of micronuclei and chromosomal aberrations in human lymphocytes by insoluble compounds of Cd(II), Hg(I), Ni(II) and Pb(II) is enhanced by NTA, 16 which also increases the frequency of micronuclei in V. jaba cells treated with insoluble Cd(II).…”

“…14 NTA also elicits the ability of PbCrO 4 to induce micronuclei and chromosomal aberrations in human lymphocytes 16 as well as DNA damage in E. coli (present results). Induction of SCE in cultured mammalian cells and of micronuclei and chromosomal aberrations in human lymphocytes by insoluble compounds of Cd(II), Hg(I), Ni(II) and Pb(II) is enhanced by NTA, 16 which also increases the frequency of micronuclei in V. jaba cells treated with insoluble Cd(II). 43 Present data indicate that, when the sensitivity of the bacterial mutation assays is increased by performing a fluctuation test on E. coli WP2 uvrA strain, a positive interaction of NTA could be demonstrated, not only with insoluble Cr(VI) (as PbCrOJ, but also with soluble Cr(VI) (K 2 Cr 2 O 7 ).…”

“…NTA was shown unable to induce: (a) gene mutations in prokaryotic (£. coli, 25 ' 26 S. typhimurium 13 ' 1 *' 21 ) and eukaryotic (Ophiostoma multiannulatum, 25 S. pombe, 13 ' 25 S. cerevisiae, 25 N. crassa 28 ) microorganisms, as well as in Drosophila 29 ' 30 and mouse lymphoma cells cultured in vitro; 31 16 However, some positive results were obtained in the above studies, regarding for instance the induction of gene mutations in E. coli 25 and Drosophila. 29 Moreover, induction of a new pigment in £.…”

Nitrilotriacetic acid (NTA) induces aneuploidy in drosophila and mouse germ‐line cells

“…NTA was negative for the following endpoints: 1) gene mutations in prokaryotes (E. coli) [Zetterberg, 1970;Stine and Hardigree, 1972;Venier et al, 19871, S . typhimurium [Loprieno et al, 19851, and eukaryotic microorganisms (Ophiosroma mulfiannulafum [Zetterberg, 19701, N . crassa [Stine and Adams, 1974]), as well as in mouse lymphoma [NTP, 19831 in Chinese hamster cells cultured in vitro [Celotti et al, 1987a1, and in D. melanogasrer (sex-linked recessive lethal germinal mutations [Kramers, 1976;Woodruff et al, 1985;Costa et al, 19881); 2) dominant lethal mutations [Epstein et al, 19721 and heritable reciprocal translocations [Jorgenson et al, 19751 in mice, micronuclei and chromosomal aberrations in cultured human lymphocytes [Montaldi et al, 1987;19881, and micronuclei in vivo in polychromatic erythrocytes in the mouse [Montaldi et al, 19881; 3) mitotic gene conversion in S . cerevisiae [Loprieno et al, 19851, DNA damage and repair in E. coli [Celotti et al, 1987b], DNA repair synthesis [Williams et al, 19821 and sister chromatid exchanges [Ved Brat and Williams 1982;Montaldi et al, 1985, 19871 in cultured mammalian cells, and sister chromatid exchanges in developing eggs of the marine mussel Mytilus galloprovincialis [Brunetti et al, 19861;4) in vitro transformation of BHK21k13 hamster cells [Lanfranchi et al, 19881. Some positive results also were obtained with NTA in short-term genotoxicity tests.…”

“…cerevisiae [Loprieno et al, 19851, DNA damage and repair in E. coli [Celotti et al, 1987b], DNA repair synthesis [Williams et al, 19821 and sister chromatid exchanges [Ved Brat and Williams 1982;Montaldi et al, 1985, 19871 in cultured mammalian cells, and sister chromatid exchanges in developing eggs of the marine mussel Mytilus galloprovincialis [Brunetti et al, 19861;4) in vitro transformation of BHK21k13 hamster cells [Lanfranchi et al, 19881. Some positive results also were obtained with NTA in short-term genotoxicity tests. The relevance of these, however, is lowered by some discrepancies and criticisms: 1) Gene mutations in human cells cultured in vitro were positive for the induction of resistance to dyphteria toxin [Grilli and Capucci, 19851, but this is not a widely used test, and the results are not confirmed using the more validated tests based on resistance to base analogues [NTP, 1983;Celotti et al, 1987al. 2) Chromosomal aberrations and/or micronuclei were observed after very long treatments with extremely high NTA concentrations in cultured cells of V. faba [Kihlman and Sturelid, 1970;De Marco et al, 19861, A. cepa [De Marco et al, 19861, rat kangaroo [Kihlman and Sturelid, 19701, and human lymphocytes [Bora, 19751; however, these results were not confirmed by more conventional treatment conditions [Montaldi et al, 1987;19881. 3) Binding to mammalian cell DNA in vitro [Colacci, 19851 and DNA damage in E. coli [Venier et al, 19871 were observed with systems not usually included among those employed to detect this kind of genetic effect, such as DNA repair synthesis and sister chromatid exchange assays, which gave absolutely negative results for NTA [Williams et al, 1982;Ved Brat and Williams, 1982;Montaldi et al, 1985;19871. 4) The efficiency of NTA in inducing mammalian cell transformation in cultured BALBk-3t3 mouse cells [Sivak, 19831 as well as in rat embryo cells infected with leukemia virus [Traul et al, 19811 is very low and borderline significant; thus, the results were scored as questionable [NTP, 19831. Therefore, it must be concluded that the weight of the evidence indicates that NTA is unable to induce direct genetic effects.…”