Induction of micronuclei in mouse bone marrow after combined X‐rays‐cyclophosphamide and X‐rays‐mitomycin C treatments

Dobrzyńska, Małgorzata M.; Gajewski, Antoni

doi:10.1002/(sici)1520-6866(1999)19:4<267::aid-tcm3>3.0.co;2-#

Cited by 5 publications

(1 citation statement)

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“…This includes the effects of the tobacco-related nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1butanone in combination with α-particle radiation in a human-hamster hybrid cell assay for toxicity and mutagenicity (23) or the combined effects of γ-radiation and ethylene oxide in human diploid fibroblasts (24). The induction of micronuclei in polychromatic erythrocytes of bone marrow of mice also was additive for the combination of X rays with cyclophosphamide or mitomycin C (25). An example for synergistic effects induced by the combination of an activationindependent alkylating agent with X rays is the induction of mutation in the Tradescantia stamen-hair system (26).…”

Section: Combined Exposure To Radiation and Chemicalsmentioning

confidence: 99%

Deviation from additivity in mixture toxicity: relevance of nonlinear dose-response relationships and cell line differences in genotoxicity assays with combinations of chemical mutagens and gamma-radiation.

Lutz

Vamvakas

Kopp‐Schneider

et al. 2002

Environ Health Perspect

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Sublinear dose-response relationships are often seen in toxicity testing, particularly with bioassays for carcinogenicity. This is the result of a superimposition of various effects that modulate and contribute to the process of cancer formation. Examples are saturation of detoxification pathways or DNA repair with increasing dose, or regenerative hyperplasia and indirect DNA damage as a consequence of high-dose cytotoxicity and cell death. The response to a combination treatment can appear to be supra-additive, although it is in fact dose-additive along a sublinear dose-response curve for the single agents. Because environmental exposure of humans is usually in a low-dose range and deviation from linearity is less likely at the low-dose end, combination effects should be tested at the lowest observable effect levels (LOEL) of the components. This principle has been applied to combinations of genotoxic agents in various cellular models. For statistical analysis, all experiments were analyzed for deviation from additivity with an n-factor analysis of variance with an interaction term, n being the number of components tested in combination. Benzo[a]pyrene, benz[a]anthracene, and dibenz[a,c]anthracene were tested at the LOEL, separately and in combination, for the induction of revertants in the Ames test, using Salmonella typhimurium TA100 and rat liver S9 fraction. Combined treatment produced no deviation from additivity. The induction of micronuclei in vitro was investigated with ionizing radiation from a 137Cs source and ethyl methanesulfonate. Mouse lymphoma L5178Y cells revealed a significant 40% supra-additive combination effect in an experiment based on three independent replicates for controls and single and combination treatments. On the other hand, two human lymphoblastoid cell lines (TK6 and WTK1) as well as a pilot study with human primary fibroblasts from fetal lung did not show deviation from additivity. Data derived from one cell line should therefore not be generalized. Regarding the testing of mixtures for deviation from additive toxicity, the suggested experimental protocol is easily followed by toxicologists.

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Section: Combined Exposure To Radiation and Chemicalsmentioning

confidence: 99%

Deviation from additivity in mixture toxicity: relevance of nonlinear dose-response relationships and cell line differences in genotoxicity assays with combinations of chemical mutagens and gamma-radiation.

Lutz

Vamvakas

Kopp‐Schneider

et al. 2002

Environ Health Perspect

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Micronucleus formation induced by the combination of low doses of X-rays and antineoplastic drugs in bone marrow of male mice

Dobrzyńska¹

2000

Teratog. Carcinog. Mutagen.

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People are widely exposed during their lifetime to many biological, chemical, and physical agents in the environment and at work. In this paper the effects of combined exposures of nonmutagenic doses of X-rays and anticancer agents (cyclophosphamide, mitomycin C, and vinblastine) have been investigated on the induction of micronuclei in the bone marrow of laboratory mice. The combination of X-rays and anticancer drugs enhanced the frequency of micronuclei in some cases. The strongest effects were found after the combination of X-rays and cyclophosphamide at 24 h and 72 h. The combined treatment of X-rays and mitomycin C enhanced the mutagenic effect at 72 h. The combination of X-rays + vinblastine slightly potentiated the mutagenic effect at 24 h and 48 h.

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In Vivo Evaluation of the Genotoxic Effects of Gonadotropins on Rat Reticulocytes

Duran

Koc

Özdemirci³

et al. 2011

Current Therapeutic Research

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Induction of micronuclei in mouse bone marrow after combined X‐rays‐cyclophosphamide and X‐rays‐mitomycin C treatments

Cited by 5 publications

References 50 publications

Deviation from additivity in mixture toxicity: relevance of nonlinear dose-response relationships and cell line differences in genotoxicity assays with combinations of chemical mutagens and gamma-radiation.

Deviation from additivity in mixture toxicity: relevance of nonlinear dose-response relationships and cell line differences in genotoxicity assays with combinations of chemical mutagens and gamma-radiation.

Micronucleus formation induced by the combination of low doses of X-rays and antineoplastic drugs in bone marrow of male mice

In Vivo Evaluation of the Genotoxic Effects of Gonadotropins on Rat Reticulocytes

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