Effects of vinblastine and colchicine on male rat meiosis in vivo: Disturbances in spindle dynamics causing micronuclei and metaphase arrest

Kallio, Marko J.; Sjöblom, Tiina; Lähdetie, Jaana

doi:10.1002/em.2850250204

Cited by 27 publications

(11 citation statements)

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“…Cyclophosphamide, an alkylating agent used in chemotherapy, requires metabolic activation before it can act as a mutagenic agent to promote chromosomal aberrations (Anderson et al, 1995). Vinblastine sulfate, an aneugenic agent derived from Vinca alkaloids and used here as a positive control, inhibits the polymerization of the tubulin dimer in vitro, thereby preventing cell proliferation at low concentrations (Kallio et al, 1995). Treatment with cyclophosphamide or vinblastine sulfate led to the death of some fish within 24 h after injection, making it impossible to analyze the same number of cells for each group (Table I).…”

Section: Discussionmentioning

confidence: 99%

Micronucleus frequencies in Astyanax bimaculatus (Characidae) treated with cyclophosphamide or vinblastine sulfate

Matsumoto

Cólus

2000

Genet. Mol. Biol.

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Two known mutagenic drugs, cyclophosphamide and vinblastine sulfate, were tested using the micronucleus test in the native fish species, Astyanax bimaculatus, in order to determine which of these drugs and the doses which would be the most adequate for use as positive controls in this species. This Brazilian fish species was chosen because few toxicity studies have used native fish species and this particular species is widely consumed in various regions of Brazil. Three thousand erythrocytes per specimen were scored. Doses of 16 and 8 mg/kg body weight of cyclophosphamide and vinblastine sulfate, respectively, were the most effective in causing micronuclei. Cyclophosphamide was the most mutagenic of the two drugs and is recommended for use as a positive control in A. bimaculatus.
Duas drogas reconhecidas como mutagênicas, ciclofosfamida e vimblastina sulfato, foram avaliadas usando o teste do micronúcleo em uma espécie de peixe nativa, Astyanax bimaculatus, para detectar que droga e quais doses são as mais adequadas para serem usadas como controles positivos para esta espécie. Esta espécie de peixe brasileira foi escolhida devido à escassez de estudos toxicológicos com espécies de peixes nativos e também porque ela é amplamente consumida em algumas regiões do Brasil. Um total de 3000 eritrócitos por espécimen foram contados. As doses de 16 e 8 mg/kg de peso corporal de ciclofosfamida e de vimblastina sulfato, respectivamente, foram as mais efetivas na indução de micronúcleos. A ciclofosfamida mostrou ser o melhor agente mutagênico para ser usado como um controle positivo para Astyanax bimaculatus

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Section: Discussionmentioning

confidence: 99%

Micronucleus frequencies in Astyanax bimaculatus (Characidae) treated with cyclophosphamide or vinblastine sulfate

Matsumoto

Cólus

2000

Genet. Mol. Biol.

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“…The potential teratogenic effect of colchicine arises from its effect on microtubules and the possible interruption of spindle formation in tissues associated with high mitotic activity (5). In a study by Shoji and Makino, the effects of colchicine on mouse embryos were investigated with special regard to the frequency of fetal malformations and death (6).…”

Section: Introductionmentioning

confidence: 99%

Pregnancy outcomes in women with Familial Mediterranean Fever receiving colchicine: Is amniocentesis justified?

Ben‐Chetrit¹,

Ben-Chetrit²,

Berkun³

et al. 2010

Arthritis Care & Research

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Objective. To evaluate the outcome of pregnancies in women with familial Mediterranean fever (FMF) who are taking colchicine, and to reconsider the justification for amniocentesis in these women. Methods. The outcome of 179 pregnancies in a group of women with FMF taking colchicine was compared with the outcome of 197 pregnancies in women with FMF who did not take colchicine during pregnancy and with 312 pregnancies in another cohort of healthy pregnant women of similar age and ethnicity.Results. There was no difference in the 3 groups regarding early abortions, late abortions, or congenital malformations. There was a mild trend towards a better outcome for the colchicine-treated group but these results did not reach statistical significance. Conclusion. Treatment with colchicine during pregnancy in patients with FMF is beneficial in controlling the disease while not affecting the outcome of the pregnancy; therefore there is no justification for recommending amniocentesis in women taking colchicine solely because of this treatment.

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“…Micronuclei in spermatids are caused by chromosome breakage and/or spindle disturbance in meiotic spermatocytes following exposure to mutagens [6,8]. Chromosome fragments or whole chromosomes detached from the spindles lag behind during anaphase, and consequently can be identified as small spherical bodies, MN, in the newly formed round spermatids [13].…”

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The Fungicide Carbendazim Induces Meiotic Micronuclei in the Spermatids of the Rat Testis.

1999

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ABSTRACT. Whether the fungicide carbendazim affects the meiotic spermatocytes and consequently induces chromosome aberrations in the spermatids was determined in the adult rat testis using the micronucleus test. Round spermatids containing micronuclei (MN) were significantly increased in number at stages I and V on days 1 and 4.5 after treatment with carbendazim (100 mg/kg), respectively (p<0.05). Immunocytochemistry indicated that approximately 68% of the carbendazim-induced MN contained kinetochores. These results suggest that carbendazim induces chromosome aberrations in spermatids with a high incidence of aneuploidy.-KEY WORDS: carbendazim, micronucleus, spermatid.J. Vet. Med. Sci. 61(5) 573-576, 1999 vascular perfusion technique. The tissue blocks were postfixed in 1% OsO 4 , dehydrated in ethanol, and embedded in Quetol 812. Sections cut at a thickness of 1 µm were stained with toluidine blue and observed using a × 100 oil immersion objective. For studies of other end points, unfixed seminiferous tubules were processed as follows. Testes were collected at the individual post-treatment intervals, and the seminiferous tubules were immediately teased apart and isolated in phosphate-buffered saline (PBS). The stages of the isolated tubules were determined under a transilluminating stereomicroscope according to the criteria of Parvinen et al. [13,14], and segments of tubules at specific stages were cut out. The segments were transferred to glass slides, overlaid with cover glasses, and gently squashed to squeeze the germ cells from the tubules. After confirmation of the steps of round spermatids under a phase-contrast microscope, the specimens were frozen in liquid nitrogen, and the cover glasses were removed. They were then fixed with 10% acetic acid in ethanol for 10 min at room temperature, followed by DNA staining with Hoechst 33258 (3 µg/ml PBS, Sigma, St. Louis, MO, U. S. A.) for 1 hr. To study the dose-dependency, 1,500 step 1 spermatids per animal were examined for the presence of MN using an Olympus BX50F4 fluorescence microscope, and their frequencies were compared among doses. To study the survival of the MN, 1,500 round spermatids per animal prepared at specific post-treatment intervals were examined. For kinetochore immunocytochemistry, tubular segments at stage I were fixed with 10% acetic acid in ethanol for 10 min. The specimens were rinsed in PBS containing 0.1% Tween 20, and then incubated initially in CREST serum (Binding Site, Birmingham, U. K.) diluted at 1:50 with PBS containing 0.1% Tween 20 overnight at room temperature. CREST serum is derived from scleroderma patients and contains the antibody to kinetochores [3,10]. As controls, sections were incubated without CREST serum. Following rinses in PBS, the specimens were incubated in FITC-conjugated rabbit anti-human IgG (1:50, Dako, Glostrup, Denmark) for 2 hr. Following counterstaining with Hoechst 33258, kinetochore

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Effects of vinblastine and colchicine on male rat meiosis in vivo: Disturbances in spindle dynamics causing micronuclei and metaphase arrest

Cited by 27 publications

References 38 publications

Micronucleus frequencies in Astyanax bimaculatus (Characidae) treated with cyclophosphamide or vinblastine sulfate

Micronucleus frequencies in Astyanax bimaculatus (Characidae) treated with cyclophosphamide or vinblastine sulfate

Pregnancy outcomes in women with Familial Mediterranean Fever receiving colchicine: Is amniocentesis justified?

The Fungicide Carbendazim Induces Meiotic Micronuclei in the Spermatids of the Rat Testis.

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