Baseline and phosphoramide mustard-induced sister-chromatid exchanges in cancer patients treated with cyclophosphamide.
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.
McDiarmid
M A
MA
Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205.
Strickland
P T
PT
Kolodner
K
K
Hansen
J
J
Jacobson-Kram
D
D
D001943:Breast Neoplasms / Q000188:drug therapy; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D010752:Phosphoramide Mustards / Q000009:adverse effects* / Q000627:therapeutic use; D012016:Reference Values; D012854:Sister Chromatid Exchange
D010752:Phosphoramide Mustards; C030090:phosphoramide mustard