Genetic toxicology of bleomycin

Vig, Baldev K.; Lewis, Roger

doi:10.1016/0165-1110(78)90019-2

Cited by 120 publications

(22 citation statements)

References 76 publications

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“…are glycopeptide antibiotics isolated from Streptomyces verticillus and are routinely used in cancer chemotherapy. These compounds exert their genotoxic effect by causing oxidative damage to DNA, which in turn leads to gene mutations, chromosomal aberrations and aneuploidy (Vig and Lewis, 1978;Povirk and Austin, 1991). CP (Enduxan, 20 mg/kg b.w.)…”

Section: Fish Treatments and Micronucleus Testmentioning

confidence: 99%

Variability in micronucleus induction with different mutagens applied to several species of fish

Grisólia

Cordeiro

2000

Genet. Mol. Biol.

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Fish are often used for screening genotoxicity of water. For such programs, a knowledge of the sensitivity to clastogens, spontaneous micronucleus frequency and cell cycle kinetics of the target tissue is necessary. To investigate the pattern of inter-specific sensitivity to micronucleus induction three species of fish, Tilapia rendalli, Oreochromis niloticus and Cyprinus carpio, were exposed to the clastogens bleomycin (BLM), cyclophosphamide (CP), 5-fluorouracil (5-FU), and mitomycin C (MMC). The binucleate/mononucleate ratio in peripheral erythrocytes exposed to cytochalasin B was also used to evaluate the time-dependent response of micronucleus formation during hematopoesis in the kidney and the micronucleus peak in peripheral erythrocytes. Micronucleus frequencies induced by CP were significantly greater than their respective controls for the three fish species throughout all treatment periods. During the whole evaluation period (30 days) CP was also the most effective clastogen. In general, until the 14th day of evaluation period T. rendalii was the most sensitive species to clastogens. No difference in micronucleus frequencies among species was observed in the 4th evaluation (at the 30th day). A micronucleus peak was observed at the 7th day after treatment. After the 14th day the frequencies were stabilized. The cytochalasin B experiment was carried out to demonstrate that micronuclei induced in the young kidney erythrocyte cells were detected in the circulating blood 2-4 days later.
Este estudo fez uma avaliação da indução de micronúcleos em eritrócitos de sangue periférico de peixes Tilapia rendalli, Oreochromis niloticus e Cyprinus carpio após o tratamento com mitomicina C, ciclofosfamida, 5-fluorouracil e bleomicina. Foram colhidas amostras periódicas de sangue com 2, 7, 14 e 30 dias após o tratamento único. Os tratamentos com citocalasina B tiveram como objetivo analisar as proporções entre células binucleadas/mononucleadas nos diferentes períodos de tratamento, para a comparação com os picos de micronúcleos entre as diferentes espécies, uma vez que o orgão hematopoiético nos peixes é o rim cefálico e o sangue analisado é de origem periférica, o que nos dá uma noção do tempo do ciclo celular dos eritrócitos. A análise das taxas de aumento das freqüências de micronúcleos ao longo do tempo demonstrou que do 2° ao 7°dias elas foram crescentes, decresceram ao 14° dia e mantiveram-se estáveis até ao 30°. Os 4 compostos químicos aumentaram significativamente as freqüências de micronúcleos ao longo de todo o período de tratamento, sendo que a ciclofosfamida e a mitomicina C foram as mais efetivas. A T. rendalli foi a espécie mais sensível a todos os tratamentos, enquanto que C. carpio foi a mais resistente. Entre 2 e 7 dias pós-tratamento observaram-se as maiores induções de micronúcleos. A partir do 14° dia de tratamento as freqüências de micronúcleos tenderam a diminuir e as diferenças entre as espécies não foram significativas

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Section: Fish Treatments and Micronucleus Testmentioning

confidence: 99%

Variability in micronucleus induction with different mutagens applied to several species of fish

Grisólia

Cordeiro

2000

Genet. Mol. Biol.

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“…Osim toga, aktivira kisik pri čemu nastaje superoksid radikal. Uzrokuje inhibiciju sinteze DNA, a u manjoj mjeri utječe na inhibiciju sinteze RNA i proteina (12,(26)(27)(28).…”

Section: Citotoksični Antibiotici I Njima Srodne Tvariunclassified

Antineoplastic Drugs as a Potential Risk Factor in Occupational Settings: Mechanisms of Action at the Cell Level, Genotoxic Effects, and Their Detection Using Different Biomarkers

Kopjar

Želježić

Kašuba

et al. 2010

Archives of Industrial Hygiene and Toxicology

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Nevenka KOPJAR, Davor ŽELJEŽIĆ, Vilena KAŠUBA i Ružica ROZGAJ Institut za medicinska istraživanja i medicinu rada, Zagreb, HrvatskaPrimljeno u siječnju 2010. Prihvaćeno u veljači 2010.U članku je prikazana osnovna podjela antineoplastičnih lijekova prema mehanizmima djelovanja na razini stanice. Objašnjeni su mehanizmi genotoksičnosti najvažnijih vrsta lijekova koji se primjenjuju u okviru uobičajenih protokola za liječenje zloćudnih novotvorina. Navedena je važeća klasifi kacija antineoplastika prema kancerogenom potencijalu, podaci o mutagenom potencijalu te je prikazana njihova podjela u skladu s anatomsko-terapijsko-kemijskim sustavom klasifi kacije. Sustavno su prikazani najvažniji rezultati svjetskih i hrvatskih istraživanja na populacijama radnika izloženih antineoplasticima, provedenih u razdoblju 1980.-2009. s pomoću četiri najčešće primjenjivane metode: analize izmjena sestrinskih kromatida, analize kromosomskih aberacija, mikronukleus-testa i komet-testa. Objašnjena su osnovna načela navedenih metoda te raspravljene njihove prednosti i nedostaci. Biološki pokazatelji daju važne podatke o individualnoj osjetljivosti profesionalno izloženih ispitanika koji mogu poslužiti unaprjeđenju postojećih uvjeta rada i upravljanju rizicima pri izloženosti genotoksičnim agensima. Na osnovi prednosti i nedostataka citogenetičkih metoda zaključeno je da je mikronukleus-test, koji podjednako uspješno dokazuje klastogene i aneugene učinke, jedna od najboljih metoda dostupnih za otkrivanje štetnih djelovanja antineoplastičnih lijekova koji su u aktivnoj primjeni.

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“…In this article, to compare the power to detect low level genotoxicity, the lowest genotoxic dose (LGD) is defined as the lowest dose at which each mutagen causes a positive response on each genotoxicity assay, i.e., a low LGD indicates a high power. BLM is well known to induce SSBs [6], which coincides well with the induction of comet-tails by BLM in the acellular and standard assays at pH 12.…”

Section: Detection Of Ssbs As Initial Lesionsmentioning

confidence: 99%

The Power of the Comet Assay to Detect Low Level Genotoxicity and DNA Repair Factors Affecting its Power

Sasaki

SatomiKawaguchi

Nakamura

2017

MOJT

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The comet assay is considered to be a rapid and sensitive procedure for quantitating DNA damage in mammalian cells. In this article, to interpret its outcomes adequately, its power to detect low level genotoxicity and factors affecting its power were reviewed. Although the development of initial lesions into alkali-labile sites and/or SSBs through repairing events is an important factor to support its detecting power, their repair reduce its power to detect SSBs as an initial DNA lesion. The acellular comet assay, in which slides with gel are prepared from untreated cells are exposed after lysis to test agents. Thus, detection of SSBs as initial lesions but not alkali-labile sites generated from DNA lesion such as alkylated bases and the power to detect low level SSBs as initial lesions is lower in the standard than in the acellular assay. The acellular comet assay would be practically used to detect SSBs as initial lesions. The inhibitors of re-synthesis andincisionsteps of the excision repair enhance and suppress comet-tail formation, respectively. Although the incision step of repairing process is necessary to support the sensitivity of the comet assay, its re-synthesis step reduces the power to detect low level genotoxicity. Although this assay can detect a wide variety of genotoxoic compounds and its power to detect genotoxicity were identical to that of the MN test, its power to detect low levels of genotoxic potential is inferior to that of the MN test. However, its power of to detect a low level of genotoxicity can be elevated to a level higher than that of the MN test by using DNA resynthesis inhibitors, such as araC and HU. In conclusion, the outcomes of comet assay should be interpretedappropriately in consideration of the action of DNA repair.

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Genetic toxicology of bleomycin

Cited by 120 publications

References 76 publications

Variability in micronucleus induction with different mutagens applied to several species of fish

Variability in micronucleus induction with different mutagens applied to several species of fish

Antineoplastic Drugs as a Potential Risk Factor in Occupational Settings: Mechanisms of Action at the Cell Level, Genotoxic Effects, and Their Detection Using Different Biomarkers

The Power of the Comet Assay to Detect Low Level Genotoxicity and DNA Repair Factors Affecting its Power

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