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Chemical mutagenesis the Chinese hamster bone marrow as an in vivo test system


Schmid, Werner; Arakaki, D T; Breslau, N A; Culbertson, J C (1971). Chemical mutagenesis the Chinese hamster bone marrow as an in vivo test system. Human Genetics, 11(2):103-118.

Abstract

Summary. 1. Endoxan and Trenimon, the alkylating agents tested, are potent cytostatic drugs, therapeutically acting through their mutagenic effects. To demonstrate their chromosome breaking effects in bone marrow, higher than the usual therapeutic doses in man had to be applied. Starting from these practical threshold doses the dose-response curves were, however, rising very steeply.
2. The extent of chromosome damage in individual cells was dose-dependent: after treatments in the lower dose range only metaphases with one or few chromatid aberrations were observed in a small percentage of the mitotic figures. With increasing doses the number of aberrations per cell steadily rose to the point of complete pulverization of the chromosome complement.
3. After the last application of the test substances the cell population with visible chromosome damage diminuishes soon. The maximum incidence of aberrations was observed after 6--8 hrs.
4, The effect was several times higher after two applications spaced by 24 hrs than after a single application. With Endoxan given per os the incidence of affected cells was 8 times higher, with Trenimon i.p. 2--3 times. A longer oral treatment is less effective due to the radiomimetic damage to the intestinal mueosa thereby reducing further resorption of the mutagenic compound. Only a relatively small increase in effect is gained with more than two intraperitoneal applications; if there is a severe mutagenic effect, the animals begin to succumb to the treatment after 4 days.
5. A prolonged treatment with low doses of Endoxan (8 mg/kg daily for 7 weeks) produced no increase in the very low aberration incidence.

Abstract

Summary. 1. Endoxan and Trenimon, the alkylating agents tested, are potent cytostatic drugs, therapeutically acting through their mutagenic effects. To demonstrate their chromosome breaking effects in bone marrow, higher than the usual therapeutic doses in man had to be applied. Starting from these practical threshold doses the dose-response curves were, however, rising very steeply.
2. The extent of chromosome damage in individual cells was dose-dependent: after treatments in the lower dose range only metaphases with one or few chromatid aberrations were observed in a small percentage of the mitotic figures. With increasing doses the number of aberrations per cell steadily rose to the point of complete pulverization of the chromosome complement.
3. After the last application of the test substances the cell population with visible chromosome damage diminuishes soon. The maximum incidence of aberrations was observed after 6--8 hrs.
4, The effect was several times higher after two applications spaced by 24 hrs than after a single application. With Endoxan given per os the incidence of affected cells was 8 times higher, with Trenimon i.p. 2--3 times. A longer oral treatment is less effective due to the radiomimetic damage to the intestinal mueosa thereby reducing further resorption of the mutagenic compound. Only a relatively small increase in effect is gained with more than two intraperitoneal applications; if there is a severe mutagenic effect, the animals begin to succumb to the treatment after 4 days.
5. A prolonged treatment with low doses of Endoxan (8 mg/kg daily for 7 weeks) produced no increase in the very low aberration incidence.

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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 > Genetics
Health Sciences > Genetics (clinical)
Uncontrolled Keywords:Genetics (clinical), Genetics, Mutagenic Effect, Chromosome Complement, Chromosome Damage, Cytostatic Drug, Chromosome Breaking
Language:English
Date:1 January 1971
Deposited On:27 Jan 2023 13:33
Last Modified:28 Apr 2024 01:47
Publisher:Springer
ISSN:0340-6717
Additional Information:Prof. Dr. med. Werner Schmid (Director of the institute till 1996)
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/bf00393791
PubMed ID:5545035
Other Identification Number:Corpus ID: 19625342