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

Abstract

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.<br>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

Mikania glomerataSprengel (Asteraceae) Influences the Mutagenicity Induced by Doxorubicin without Altering Liver Lipid Peroxidation or Antioxidant Levels

“…Other studies also demonstrated an interaction of different agents, including secondary metabolites and crude extracts of plants, resulting in enhanced risk for genotoxicity (Ansah et al 2005;Araújo et al 1998), similar to the organic tomato extract that enhanced genotoxicity induced by DXR in the Drosophila wing spot test (Dutra et al 2009). …”

Genotoxic Effects of the Alkaloids Harman and Harmine Assessed by Comet Assay and Chromosome Aberration Test in Mammalian Cells in vitro

“…In agreement with all these observations, the cytotoxic and genotoxic effects of these b-carboline alkaloids have been related to their injurious action on DNA (Sasaki et al 1992;Shimoi et al 1992;Meester 1995;Picada et al 1997) because of the intercalation of DNA (Meester 1995;Taira et al 1997;Balon et al 1999). Intercalating agents such as acridine and quinacrine stains, as well as antineoplastic agents, can induce chromosome aberrations and DNA strand breaks in mammalian cells (De Marini & Laurence 1992;Suzuki et al 1995;Araú jo et al 1998;Palitti 1998). Moreover, many intercalating agents are DNA topoisomerase inhibitors and can interfere with the breakage-rejoining action of these enzymes, resulting in the formation of complexes between enzyme and DNA, favoring DNA strand breaks (Chen & Liu 1994;Wang 1996Wang & 1998Hammonds et al 2000).…”