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Hypoxanthine phosphoribosyltransferase: HPRT gene

  • A membrane-situated salvage enzyme which transfers purines such as hypoxanthine back into the intracellular nucleic acid precursor pool.
  • A non-essential enzyme (in lymphocytes); so mutations are not lethal and can accumulate in the lymphocyte pool.
  • The HPRT gene lies on the X chromosome, so only one functional copy is present in each cell, and a single mutational event can make a cell hprt--.
  • Cells (usually lymphocytes) are incubated at fairly low density in cell culture medium. Mutant cells are selected by incubating with the toxic purine analogue 6-thioguanine which kills wild-type cells. Survivors form clones which are counted.

There is apparently an inverse correlation between HPRT mutant frequency and plasma vitamin C. But smokers tend to have higher MFs and lower vitamin C. This is a nice example of smoking as a confounding factor.