Sister chromatid exchanges in human lymphocytes exposed to single cytotoxic drugs in vivo or in vitro.
Venous blood was taken from apparently healthy volunteers and patients with cancer, the latter both before and at intervals after treatment with single cytotoxic drugs. Cells from untreated individuals were exposed to a range of concentrations of drugs in culture medium. Chlorambucil, treosulfan and cyclophosphamide (activated by hepatic microsomes) significantly increased the numbers of SCEs, both in vitro and in the lymphocytes of patients. While methotrexate and 5-fluorouracil had no effect, bleomycin slightly increased the number of SCEs, but only in vitro. Although the in vitro dose-effect relationship indicated which drugs would increase the frequency of SCE in vivo, the magnitude of the response tended to be overestimated. When patients were treated with drugs the frequency of SCE increased, then declined with time. Though this complicates the quantitative relationship between dose and damage, SCEs may be useful to monitor the effects of alkylating agents on normal tissues.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002066:Busulfan / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D002699:Chlorambucil / Q000494:pharmacology; D003434:Crossing Over, Genetic / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000970:Antineoplastic Agents; D002699:Chlorambucil; D003520:Cyclophosphamide; C018404:treosulfan; D002066:Busulfan