Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1991 Nov;95:205–210. doi: 10.1289/ehp.9195205

Arsenite as the probable active species in the human carcinogenicity of arsenic: mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler's solution.

H Tinwell 1, S C Stephens 1, J Ashby 1
PMCID: PMC1568403  PMID: 1821373

Abstract

Sodium arsenite, potassium arsenite, and Fowler's solution (arsenic trioxide dissolved in potassium bicarbonate) are equally active in the mouse bone marrow micronucleus assay (approximately 10 mg/kg by IP injection). The natural ore orpiment (principally As2S3) was inactive despite blood levels of arsenic of 300 to 900 ng/mL in treated mice at 24 hr. Sodium arsenite was active in three strains of mice. It is suggested that the human lung cancer observed among arsenic ore smelters and the skin cancer among people exposed therapeutically to Fowler's solution, have, as their common origin, the genotoxic arsenite ion AsO2-. The difficulty experienced when attempting to demonstrate rodent carcinogenicity for derivatives of arsenic suggests that the bone marrow micronucleus assay may act as a useful assay for potentially carcinogenic arsenic derivatives.

Full text

PDF
207

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arrouijal F. Z., Hildebrand H. F., Vophi H., Marzin D. Genotoxic activity of nickel subsulphide alpha-Ni3S2. Mutagenesis. 1990 Nov;5(6):583–589. doi: 10.1093/mutage/5.6.583. [DOI] [PubMed] [Google Scholar]
  2. Ashby J., Mirkova E. Re-evaluation of the need for multiple sampling times in the mouse bone marrow micronucleus assay: results for DMBA. Environ Mol Mutagen. 1987;10(3):297–305. doi: 10.1002/em.2850100308. [DOI] [PubMed] [Google Scholar]
  3. Ashby J. The efficient preparation of corn oil suspensions. Mutat Res. 1987 Jan;187(1):45–45. doi: 10.1016/0165-1218(87)90075-9. [DOI] [PubMed] [Google Scholar]
  4. Cuzick J., Evans S., Gillman M., Price Evans D. A. Medicinal arsenic and internal malignancies. Br J Cancer. 1982 Jun;45(6):904–911. doi: 10.1038/bjc.1982.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Deknudt G., Léonard A., Arany J., Jenar-Du Buisson G., Delavignette E. In vivo studies in male mice on the mutagenic effects of inorganic arsenic. Mutagenesis. 1986 Jan;1(1):33–34. doi: 10.1093/mutage/1.1.33. [DOI] [PubMed] [Google Scholar]
  6. Eastmond D. A., Tucker J. D. Identification of aneuploidy-inducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody. Environ Mol Mutagen. 1989;13(1):34–43. doi: 10.1002/em.2850130104. [DOI] [PubMed] [Google Scholar]
  7. Eaton D. K., Holcombe J. A. Oxygen ashing and matrix modifiers in graphite furnace atomic absorption spectrometric determination of lead in whole blood. Anal Chem. 1983 May;55(6):946–950. doi: 10.1021/ac00257a030. [DOI] [PubMed] [Google Scholar]
  8. Hildebrand H. F., D'Hooghe M. C., Shirali P., Bailly C., Kerckaert J. P. Uptake and biological transformation of beta NiS and alpha Ni3S2 by human embryonic pulmonary epithelial cells (L132) in culture. Carcinogenesis. 1990 Nov;11(11):1943–1950. doi: 10.1093/carcin/11.11.1943. [DOI] [PubMed] [Google Scholar]
  9. Léonard A., Lauwerys R. R. Carcinogenicity, teratogenicity and mutagenicity of arsenic. Mutat Res. 1980 Jan;75(1):49–62. doi: 10.1016/0165-1110(80)90027-5. [DOI] [PubMed] [Google Scholar]
  10. Pershagen G., Björklund N. E. On the pulmonary tumorigenicity of arsenic trisulfide and calcium arsenate in hamsters. Cancer Lett. 1985 May;27(1):99–104. doi: 10.1016/0304-3835(85)90013-8. [DOI] [PubMed] [Google Scholar]
  11. Poma K., Degraeve N., Kirsch-Volders M., Susanne C. Cytogenetic analysis of bone marrow cells and spermatogonia of male mice after in vivo treatment with arsenic. Experientia. 1981 Feb 15;37(2):129–130. doi: 10.1007/BF01963187. [DOI] [PubMed] [Google Scholar]
  12. Shelby M. D. The genetic toxicity of human carcinogens and its implications. Mutat Res. 1988 Jan;204(1):3–15. doi: 10.1016/0165-1218(88)90113-9. [DOI] [PubMed] [Google Scholar]
  13. Shelby M. D., Zeiger E. Activity of human carcinogens in the Salmonella and rodent bone-marrow cytogenetics tests. Mutat Res. 1990 Jun-Aug;234(3-4):257–261. doi: 10.1016/0165-1161(90)90022-g. [DOI] [PubMed] [Google Scholar]
  14. Tinwell H., Ashby J. Activity of the human carcinogen MeCCNU in the mouse bone marrow micronucleus assay. Environ Mol Mutagen. 1991;17(3):152–154. doi: 10.1002/em.2850170303. [DOI] [PubMed] [Google Scholar]
  15. Tinwell H., Ashby J. Comparison of acridine orange and Giemsa stains in several mouse bone marrow micronucleus assays--including a triple dose study. Mutagenesis. 1989 Nov;4(6):476–481. doi: 10.1093/mutage/4.6.476. [DOI] [PubMed] [Google Scholar]
  16. Tinwell H., Bandara L., Ashby J. Activity of DMBA, DMH and CP in triple- and single-dose rodent bone-marrow micronucleus assays. Mutat Res. 1990 Jun-Aug;234(3-4):195–198. doi: 10.1016/0165-1161(90)90015-g. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES