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Ten model mutagens evaluated by the micronucleus test


Maier, P; Schmid, Werner (1976). Ten model mutagens evaluated by the micronucleus test. Mutation Research - Section on Environmental Mutagenesis and Related Subjects, 40(4):325-337.

Abstract

The following ten mutagenic compounds were subjected to the micronucleus bone marrow test (MNT) in the mouse: cyclophosphamide (CTX), thiotepa (TT), vincristin (VCR), colcemid (COLC), adriamycin (AM), bleomycin (BM), cytosin arabinoside (ARA C), 6-mercaptopurine (6-MP), methotrexate (MTX) and 5-fluorouracil (5-FU). Dose-effect curves were established for all compounds. With the exception of CTX, COLC and AM, the drugs also were subjected to chromosome analyses on Chinese hamster fibroblasts in vitro.

The MNT revealed loss of chromatin due to chromosome breakage and rearrangements by CTX, TT and AM, to breakage by ARA C, 6-MP, MTX and 5-FU, as well as loss of entire chromosomes caused by impairment of the spindle by VCR and COLC. With the exception of BM, the effects were demonstrable in the therapeutic dose range.

The MNT, provided it is carried out by the methodology of the authors, not only reveals chromatin loss but permits important conclusions in regard to the proliferative state of the bone marrow and the specific time of action of the mutagens in the cell cycle. If arrest of the cell cycle occurs, as in the case of anti-metabolites MTX and 5-FU particularly, the routine scheme of investigation needs to be modified since micronucleated cells appear only after release of the metabolic block, i.e. after a delay of 24 h.

The negative bone marrow results obtained with BM emphasize the importance of combining in vivo and in vitro tests.

Abstract

The following ten mutagenic compounds were subjected to the micronucleus bone marrow test (MNT) in the mouse: cyclophosphamide (CTX), thiotepa (TT), vincristin (VCR), colcemid (COLC), adriamycin (AM), bleomycin (BM), cytosin arabinoside (ARA C), 6-mercaptopurine (6-MP), methotrexate (MTX) and 5-fluorouracil (5-FU). Dose-effect curves were established for all compounds. With the exception of CTX, COLC and AM, the drugs also were subjected to chromosome analyses on Chinese hamster fibroblasts in vitro.

The MNT revealed loss of chromatin due to chromosome breakage and rearrangements by CTX, TT and AM, to breakage by ARA C, 6-MP, MTX and 5-FU, as well as loss of entire chromosomes caused by impairment of the spindle by VCR and COLC. With the exception of BM, the effects were demonstrable in the therapeutic dose range.

The MNT, provided it is carried out by the methodology of the authors, not only reveals chromatin loss but permits important conclusions in regard to the proliferative state of the bone marrow and the specific time of action of the mutagens in the cell cycle. If arrest of the cell cycle occurs, as in the case of anti-metabolites MTX and 5-FU particularly, the routine scheme of investigation needs to be modified since micronucleated cells appear only after release of the metabolic block, i.e. after a delay of 24 h.

The negative bone marrow results obtained with BM emphasize the importance of combining in vivo and in vitro tests.

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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 November 1976
Deposited On:26 Jan 2023 06:51
Last Modified:28 Apr 2024 01:46
Publisher:Elsevier
ISSN:0165-1161
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/0165-1218(76)90031-8
PubMed ID:64925