Measurement of HPRT mutant frequencies in T-lymphocytes from healthy human populations

R. F. Branda, L. M. Sullivan, J. P. O'Neill, M. T. Falta, J. A. Nicklas, B. Hirsch, P. M. Vacek, R. J. Albertini

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76 Scopus citations

Abstract

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning technique in healthy human populations. A statistical analysis was performed of assays from 232 individuals (77 males and 155 females) ranging in age from 19 to 80 years. Data from 4 donor groups were compiled: (a) 132 participants in a study of identical and fraternal twins; (b) 17 health care workers studied as part of an assessment of the risks of handling chemotherapeutic drugs; (c) 62 women with benign breast masses; and (d) 21 normal laboratory and office personnel. The relationship between age and mutant frequency (MF) was expressed by the equation: In MF = 1.46 + 0.018 age (P<0.001). Thus, MF increased by about 2% per year. Increases in cloning efficiency (CE) reduced the MF, as shown in the equation: In MF = 2.91-1.32 CE (P<0.001). CE was significantly related to age (CE = 0.47-0.002 age, P = 0.038), and the interdependent relationship between MF, age and CE expressed by the equation: In MF = 1.99-1.13 CE + 0.016 age was significant at the P<0.001 level. There was no statistically significant effect of donor gender or smoking history on MF in our population, but CE was significantly lower in males (P< 0.001). These findings confirm the importance of age and CE as factors which influence the thioguanine-resistant MF in circulating T-lymphocytes from normal adults.

Original languageEnglish (US)
Pages (from-to)267-279
Number of pages13
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume285
Issue number2
DOIs
StatePublished - Feb 1993

Bibliographical note

Funding Information:
Supported by grants from the National Cancer Institute (CA 41843, CA 30688 and P30 CA22435), the National Institute of Health (AG06886) and by EPA Cooperative Agreement No. CR-812837. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. This article has not been subjected to U.S. Environmental Protection Agency review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

Keywords

  • 6-Thioguanine-resistant
  • HPRT
  • Human population monitoring
  • T-lymphocytes

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