Effects of treatment with mitoxantrone in combination with novobiocin, caffeine and ara-C on human lymphocytes in culture

Combined radiation and antineoplastic drug treatment have important applications in cancer therapy. In the present work, an evaluation was made of two known topoisomerase II inhibitors, doxorubicin (DXR) and mitoxantrone (MXN), with g-radiation. The effects of DXR or MXN on g-radiation-induced chromosome aberrations in Chinese hamster ovary (CHO) cells were analyzed. Two concentrations of each drug, 0.5 and 1.0 µg/ml DXR, and 0.02 and 0.04 µg/ml MXN, were applied in combination with two doses of g-radiation (20 and 40 cGy). A significant potentiating effect on chromosomal aberrations was observed in CHO cells exposed to 1.0 µg/ml DXR plus 40 cGy. In the other tests, the combination of g-radiation with DXR or MXN gave approximately additive effects. Reduced mitotic indices reflected higher toxicity of the drugs when combined with radiation.
A associação de radiação ionizante com drogas antineoplásicas tem importante aplicação na terapia do câncer. No presente trabalho, foram avaliados os efeitos de dois inibidores de topoisomerase II, doxorubicina (DXR) e mitoxantrona (MXN), sobre as aberrações cromossômicas induzidas pelas radiações-g em células do ovário de hamster chinês (CHO). Foram usadas as concentrações 0,5 e 1,0 mg/ml de DXR e 0,02 e 0,04 mg/ml de MXN, combinadas com duas doses de radiações gama (20 e 40 cGy). Um significativo efeito potenciador das aberrações cromossômicas foi observado em células CHO tratadas com 1,0 mg/ml de DXR e expostas a 40 cGy de radiação. Nos outros testes, a combinação da radiação-g com a DXR ou MXN apresentou um efeito próximo ao aditivo. A redução dos índices mitóticos refletiu a alta citotoxicidade das drogas quando combinadas às radiações-g

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Chromosome damage induced by DNA topoisomerase II inhibitors combined with g-radiation in vitro

Araújo

Dias

Cecchi

et al. 1998

Genet. Mol. Biol.

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Influence of novobiocin on <FONT FACE=Symbol>g</font>-irradiation G0-lymphocytes as analyzed by cytogenetic endpoints

Savoldi-Barbosa¹,

Sakamoto-Hojo²,

Takahashi³

1999

Genet. Mol. Biol.

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Experiments with novobiocin (NB) post-treatment were performed to verify its effect on the frequencies of micronuclei (MN) and chromosomal aberrations (CA) induced by γ-irradiation (0.75, 1.5 and 3.0 Gy) in human lymphocytes at G 0 -phase. The frequencies of MN significantly decreased by 44 and 50%, for the treatment with NB 50 µg/ml (30-min pulse) after radiation doses of 1.5 and 3.0 Gy, respectively. However, CA frequencies were not significantly affected. No significant effect on CA was observed when lymphocyte cultures were exposed to a single dose of 2.0 Gy at the G 0 -phase and posttreated with 25 µg/ml NB for three hours either immediately after irradiation (G 0 -phase) or after 24 h (S-phase). The significant suppressive effect of NB on MN frequencies supports the hypothesis that NB interaction with chromatin increases access to DNA repair enzymes.

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Effects of treatment with mitoxantrone in combination with novobiocin, caffeine and ara-C on human lymphocytes in culture

Cited by 2 publications

References 24 publications

Chromosome damage induced by DNA topoisomerase II inhibitors combined with g-radiation in vitro

Chromosome damage induced by DNA topoisomerase II inhibitors combined with g-radiation in vitro

Influence of novobiocin on <FONT FACE=Symbol>g</font>-irradiation G0-lymphocytes as analyzed by cytogenetic endpoints

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