Lymphocyte Chromosome Studies in Humans Exposed to Chemical Mutagens. The Validity of the Method in 67 Patients Under Cytostatic Therapy

Eighty-three lymphocyte cultures from 67 patients exposed to high therapeutic doses of chemical mutagens and from 10 healthy controls were examined for structural aberrations of the chromatid type (gaps, breaks and exchanges) and chromosome type (rings, dicentrics, acentric fragments and abnormal chromosomes) in order to evaluate the reliability of this testing system. Most of the patients had received several drugs; a few had radiotherapy as well. Owing to insufficient yields of mitoses at shorter incubation periods a culture time of 72 h had to be chosen. Whenever possible, 100 mitoses were analyzed. Because evaluation is highly subjective, gaps (i.e. interruptions of the chromatid structure not clearly exceeding a chromatid's width) were not included in the results. The incidence of chromatid breaks was 0--2% in the controls and 0--4% in most of the patients. In 6 cases containing 5--15% mitoses with chromatid breaks and exchanges, these values did not correlate with increased incidences of chromosome type aberrations. The incidence of chromosome type aberrations was 0--1% in the controls as well as in 19/20 patients who had received anti-metabolites and spindle poisons only and in 22/53 patients who had received therapeutic irradiation and/or well-known clastogenic agents. From these findings it is concluded that an increased incidence of chromatid breaks and exchanges is not a typical finding in lymphocyte cultures of persons exposed in vivo to chromosome breaking agents, and that a normal incidence of chromosome type aberrations does not exclude exposure to massive doses of clastogens. This testing system is therefore judged to be inadequate for monitoring weak or questionable mutagens in exposed populations.