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Lymphocyte chromosome studies in humans exposed to chemical mutagens: The validity of the method in 67 patients under cytostatic therapy


Schinzel, Albert; Schmid, Werner (1976). Lymphocyte chromosome studies in humans exposed to chemical mutagens: The validity of the method in 67 patients under cytostatic therapy. Mutation Research - Mutation Research Letters, 40(2):139-165.

Abstract

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 1920 patients who had received anti-metabolites and spindle poisons only and in 2253 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.

Abstract

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 1920 patients who had received anti-metabolites and spindle poisons only and in 2253 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Toxicology
Life Sciences > Genetics
Uncontrolled Keywords:Genetics, Toxicology
Language:English
Date:1 April 1976
Deposited On:26 Jan 2023 14:09
Last Modified:05 Jun 2024 14:25
Publisher:Elsevier
ISSN:0165-7992
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/0165-1218(76)90009-4
PubMed ID:934177
Other Identification Number:Corpus ID: 33561187