Baseline and phosphoramide mustard-induced sister-chromatid exchanges in cancer patients treated with cyclophosphamide

Melissa A. McDiarmid, Paul Timothy Strickland, Ken Kolodner, John Hansen, David Jacobson-Kram

Research output: Contribution to journalArticle

Abstract

Determinations of baseline sister-chromatid exchanges (SCE) have been used extensively as indicators of previous mutagen exposure in both animals and humans. Hypersensitivity to mutagen-induced SCE levels has also been studied in a variation on the basic technique as an indication of previous mutagen exposure in a stressed or provocative test system. The genotoxicity of the alkylating anti-cancer drugs including cyclophosphamide (CP) has been examined previously by determining baseline SCEs in peripheral blood lymphocytes from treated cancer patients. This study examined the in-vivo genotoxic effects of CP therapy by comparing baseline and phosphoramide mustard (PM)-induced SCEs in therapeutically (in-vivo) treated cancer patients with SCE levels in newly diagnosed, but not treated patients. Therapeutically treated patients showed statistically higher baseline SCE frequencies than untreated control patients with a mean SCE/cell of 6.95 vs. 5.25, p <0.016. When net SCE values (induced minus baseline) were determined in PM-exposed cells in-vitro both at low dose (0.1 μg/ml PM) and high dose (0.25 μg/ml PM) however, the difference was not significant between therapeutically treated and untreated control patients. The return to control SCE levels as a function of time since last therapeutic treatment was also evaluated and no difference was found between the rate of decline of PM-induced SCEs and baseline SCE levels over time.

Original languageEnglish (US)
Pages (from-to)273-278
Number of pages6
JournalMutation Research/Genetic Toxicology
Volume241
Issue number3
DOIs
Publication statusPublished - 1990

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Keywords

  • Alkylating anti-cancer drugs
  • Baseline SCEs
  • Cyclophosphamide
  • Phosphoramide mustard-induced SCEs

ASJC Scopus subject areas

  • Genetics
  • Toxicology
  • Medicine(all)

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