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

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 less than 0.016. When net SCE values (induced minus baseline) were determined in PM-exposed cells in-vitro both at low dose (0.1 microgram/ml PM) and high dose (0.25 microgram/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.
AuthorsM A McDiarmid, P T Strickland, K Kolodner, J Hansen, D Jacobson-Kram
JournalMutation research (Mutat Res) Vol. 241 Issue 3 Pg. 273-8 (Jul 1990) ISSN: 0027-5107 [Print] Netherlands
PMID2366806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Phosphoramide Mustards
  • phosphoramide mustard
Topics
  • Breast Neoplasms (drug therapy)
  • Cells, Cultured
  • Female
  • Humans
  • Leukemia (drug therapy)
  • Lymphocytes (drug effects)
  • Male
  • Neoplasms (drug therapy)
  • Phosphoramide Mustards (adverse effects, therapeutic use)
  • Reference Values
  • Sister Chromatid Exchange

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