Measurement of mutation frequency at the HPRT locus in peripheral lymphocytes. Is this a good method to evaluate a cancer risk in pediatric patients?

Adv Exp Med Biol. 1998:431:681-6. doi: 10.1007/978-1-4615-5381-6_132.

Abstract

Validity of measurement of somatic cell mutation frequency (Mf) at the hprt locus for evaluating cancer risk of the given individual was determined in pediatric patients. Peripheral lymphocytes (PL) from patients with various diseases, including acute lymphoblastic leukemia (ALL) and Hodgkin's disease (HD), DNA repair deficient syndromes or short stature receiving growth hormone (GH), were isolated through Ficoll-Hypaque sedimentation with informed consent. Mf at the hprt locus of PL was determined by limiting dilution assay using 6-thioguanine (6-TG). Results were as follows. (1) ALL patients after chemotherapy had higher Mf than that of age-matched controls. (2) Patients with HD tended to have higher Mf after chemotherapy. (3) Among DNA-repair deficient syndromes, diseases which are susceptible to cancer (Xeroderma pigmentosum, Ataxia telangiectasia) have high Mf, but those without any cancer disposition (Cockayne syndrome, Rothmund-Thomson syndrome) have normal Mf. (4) GH-receiving patients have normal Mf, regardless of total doses of GH. Measurement of Mf at HPRT locus may be useful for evaluating cancer risk of pediatric patients.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Child
  • Child, Preschool
  • Cockayne Syndrome / drug therapy
  • DNA Damage
  • DNA Repair*
  • Hodgkin Disease / blood
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / enzymology
  • Human Growth Hormone / adverse effects*
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics*
  • Infant
  • Lymphocytes / enzymology*
  • Mutation*
  • Neoplasms / chemically induced
  • Neoplasms / epidemiology*
  • Neoplasms, Second Primary / chemically induced
  • Neoplasms, Second Primary / epidemiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Risk Factors
  • Xeroderma Pigmentosum / drug therapy

Substances

  • Human Growth Hormone
  • Hypoxanthine Phosphoribosyltransferase