A concerted approach to the study of the aneuploidogenic properties of two chelating agents (EDTA and NTA) in the germ and somatic cell lines of Drosophila and the mouse.

The genetic effects of nitrilotriacetic acid (NTA) and ethylenedinitrilotetraacetic acid (EDTA), two widely used chelating agents, were investigated by using a somatic mutation and recombination test (SMART) after treatment of larvae and the FIX test for aneuploidy after treatment of adult female Drosophila melanogaster. Chloral hydrate (CH) and 5-fluorodeoxyuridine (FdUr) were used as positive controls. Effectively absorbed amounts of the test compounds assayed in Drosophila were estimated at the single fly level by a method using 3H-leucine. NTA and EDTA were also assayed in tests for aneuploidy based on chromosome counting in mouse germ and somatic cells. We previously showed that NTA was able to induce aneuploidy (chromosomal gain) in the germ cells of both Drosophila and the mouse when tested at the exposure levels of 5 x 10(-2) M and 275 mg per kg body weight, respectively [Costa et al., Environ Mol Mutagen 12:397-407, 1988]. In the present experiments, EDTA was assayed at 2.5 x 10(-2) M and 7.5 x 10(-3) M in the FIX test adopting a three-stage brooding scheme. Significant increases (with respect to controls) in chromosomal loss were observed in the second brood and in the combined three-brood total for both exposure levels of EDTA. In the SMART test, treatments with EDTA in the same exposure range produced negative results over all end-points, whereas significant increases in the frequency of small single spots (possibly due to aneuploidy) were produced by NTA 5 x 10(-2) M. In the cytogenetic assays for aneuploidy both in the germ and somatic cells of the mouse, negative results were also obtained following the i.p. administration of 93 and 186 mg EDTA per kg b.w. The previously observed induction of germ cell aneuploidy by NTA (275 mg per kg b.w.) was confirmed in the present experiments on a different strain of mice. NTA (138-275 mg per kg b.w.) did not induce aneuploidy in somatic cells of the mouse [Russo et al., Mutat Res 226: 111-114, 1989], however. These results are compared and discussed with reference to the characteristics of the different test systems used and to the different chelating properties of NTA and EDTA.