Sister chromatid exchange and chromosome aberration analyses in mice after in vivo exposure to acrylonitrile, styrene, or butadiene monoxide
Yousuf ShariefArthur BrownLorraine C. BackerJames A. CampbellBarbara Westbrook‐CollinsAndrew G. SteadJames W. Allen
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Abstract The use of polymers in plastic and rubber products has generated concern that monomers potentially active in biological systems may be eluted from these substances. We have evaluated two such monomers, acrylonitrile and styrene, for the induction of chromosome damage in mice. Butadiene monoxide, a presumed metabolite of a third important monomer, 1,3‐butadiene, was also tested. These chemicals were administered as a single intraperitoneal injection; sister chromatid exchanges and chromosome aberrations were analyzed in bone marrow cells. Acrylonitrile and styrene were largely negative for these endpoints when tested at doses ranging to 60 mg/kg and 1,000 mg/kg, respectively. Butadiene monoxide, which previously has not been tested in a mammalian system, was determined to be a very effective inducer of sister chromatid exchanges and chromosome aberrations. Both endpoints showed a clear dose response and a greater than ten‐fold increase over control levels at high doses. These studies represent an initial step in our efforts to evaluate genetic risk associated with exposure to common polymeric chemicals.Keywords:
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A negative correlation has been established when comparing the data on sister chromatid exchange frequency and DNA repair capabilities of lymphocytes in patients with non-specific inflammatory pulmonary diseases. The role of DNA repair mechanisms in the alteration of sister chromatid exchange frequency in lymphocytes is discussed.
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Data are presented establishing a direct correlation between 3-aminobenzamide-induced sister chromatid exchange (SCE) frequency and the level of bromodeoxyuridine (BrdU) incorporated into DNA. In addition, it is shown that most of the SCEs are induced in the second cell cycle, in which BrdU-containing DNA is used as the template for replication.
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The investigation has been carried out on cultures grown in the presence of 5 x 10(-1) - 5 x 10(-5) M acrylonitrile with or without a rat liver metabolizing system (S-9 mix). The results obtained showed that acrylonitrile was toxic starting from the 5 x 10(-3) M concentration, caused a significant increase in the sister chromatid exchange (SCE) frequency in comparison with the controls (p less than or equal to 0.001) when the concentration was 5 x 10(-4) M, and elicited reparative deoxyribonucleic acid (DNA) synthesis, determined by tritiated thymidine uptake, particularly when the concentration was 5 x 10(-1) M. These effects were observed in lymphocytes of different donors and after drug activation by the S-9 mix metabolizing system.
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Sister chromatid exchange observed in metaphase chromosomes has been shown to be a sensitive assay for the detection of possible mutagenic and/or carcinogenic agents. The semisynthetic progestin medroxyprogesterone acetate is a drug used in high doses for the treatment of advanced breast cancer. We studied the frequency of sister chromatid exchange in PHA-stimulated peripheral lymphocytes of 11 patients who received medroxyprogesterone acetate in high doses. Overall results disclosed no significant effect of this drug on the frequency of sister chromatid exchange (SCE) and cell proliferation in sister chromatid differentiation patterns. Considering sex differences a slight tendency towards SCE increase and growth delay was observed in females.
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An in vivo system for differentially stained sister chromatids by incorporating 5' Bromo 2' deoxyuridine at two consecutive round of DNA replication has been developed in C. punctatus. The base line developed frequency of sister chromatid exchanges (SCEs) was found to be 0.038 SCE/chromosome. This low baseline frequency of SCEs could be useful in detecting genotoxicity of pollutants in aquatic medium.
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