Quantitative and molecular analyses of genetic risk: A study with lonizing radiation

A. W. Hsie, Z. Xu, Yongjia Yu, J. An, M. L. Meltz, J. L. Schwartz, P. Hrelia

Research output: Contribution to journalArticle

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Abstract

Mammalian cells in culture have been used to study the genetic effects of physical and chemical agents. We have used Chinese hamster ovary (CHO) cells, clone K1-BH4, to quantify mutations at the X-linked, large (35 kb) hypoxanthine-guanine phosphoribosyltransferase (hprt) locus (the CHO/HPRT assay) induced by environmental agents. By transfecting an hprt-deletion mutant CHO cell line with the plasmid vector p8V gpt, we isolated a transformant, AS52. AS52 cells carry a single functional copy of an autosomal, small (456 bp) xanthine-guanine phosphoribosyltransferase (gpt) gene (the bacterial equivalent of the mammalian hprt gene; AS52/GPT assay). We found that ionizing radiations such as X-rays and neutrons and oxidative genotoxic chemicals such as Adriamycin, bleomycin, hydrogen peroxide, and potassium superoxide are much more mutagenic to the gpt gene in AS52 cells than to the hprt locus in K1-BH4 cells. The hypermutability of the gpt gene probably results from a higher recovery of multilocus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced mutants. These results demonstrate that the use of the hprt locus alone could lead to an underestimate of the genetic risk of these agents. Analyses of the mutation spectrum using a polymerase chain reaction-based deletion screening and DNA sequencing procedure showed that a high proportion of HPRT- and GPT- mutants induced by X-rays carry deletion mutations. Thus, both the mutant frequency and mutation spectrum need to be considered in assessing the genetic risk of ionizing radiation and oxidative genotoxic chemicals.

Original languageEnglish (US)
Pages (from-to)213-218
Number of pages6
JournalEnvironmental Health Perspectives
Volume101
Issue numberSUPPL. 3
StatePublished - 1993

Fingerprint

Hypoxanthine Phosphoribosyltransferase
Molecular Biology
Radiation
mutation
gene
Genes
Cricetulus
assay
Ovary
Ionizing radiation
Ionizing Radiation
plasmid
hydrogen peroxide
polymerase chain reaction
clone
Assays
Clone cells
potassium
Cells
X-Rays

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Hsie, A. W., Xu, Z., Yu, Y., An, J., Meltz, M. L., Schwartz, J. L., & Hrelia, P. (1993). Quantitative and molecular analyses of genetic risk: A study with lonizing radiation. Environmental Health Perspectives, 101(SUPPL. 3), 213-218.

Quantitative and molecular analyses of genetic risk : A study with lonizing radiation. / Hsie, A. W.; Xu, Z.; Yu, Yongjia; An, J.; Meltz, M. L.; Schwartz, J. L.; Hrelia, P.

In: Environmental Health Perspectives, Vol. 101, No. SUPPL. 3, 1993, p. 213-218.

Research output: Contribution to journalArticle

Hsie, AW, Xu, Z, Yu, Y, An, J, Meltz, ML, Schwartz, JL & Hrelia, P 1993, 'Quantitative and molecular analyses of genetic risk: A study with lonizing radiation', Environmental Health Perspectives, vol. 101, no. SUPPL. 3, pp. 213-218.
Hsie, A. W. ; Xu, Z. ; Yu, Yongjia ; An, J. ; Meltz, M. L. ; Schwartz, J. L. ; Hrelia, P. / Quantitative and molecular analyses of genetic risk : A study with lonizing radiation. In: Environmental Health Perspectives. 1993 ; Vol. 101, No. SUPPL. 3. pp. 213-218.
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