Ascorbic Acid Modulates Doxorubicin and Cyclophosphamide-Induced Cytogenetic Damages in Sarcoma 180 Cells

Abstract

Cancer is a public health global problem. Cyclophosphamide (CPA) and Doxorubicin (DOX) are used in chemotherapy, especially by generating reactive oxygen species. The clinical use of ascorbic acid during chemotherapy also raises several controversies due to its antagonistic effects on antineoplastic agent. In this sense, this study aims to evaluate the effects of ascorbic acid (2 µg/mL) on the modulation of cytogenetic damage induced by CPA (20 µg/mL) and DOX (2 µg/ mL), as well as their interaction (AC protocol) on Sarcoma 180 tumor cells. Cytogenetic damage classified as apoptosis, necrosis, micronuclei, buds and nucleoplasmic bridges were linked to the CytokinesisBlock Micronucleus Assay application. CPA and DOX induce significant (p<0.05) increases in apoptosis, necrosis and micronuclei in the cell types tested. The damage on Sarcoma 180 cells was modulated by ascorbic acid with percentage modulation in more than 70% of CPA relative to apoptosis and micronuclei, and 32% to necrosis. The damage of DOX has been modulated by 70% to apoptosis, 40% to necrosis, rather than micronuclei, whereas, in AC protocol, modulations were observed by 52% to apoptosis and 32% and 40% to necrosis and micronuclei, respectively. There was no significance in relation to the nuclear buds and nucleoplasmic bridges. In addition, ascorbic acid did not show any effect. These results are other studies, which indicate hazards to chemotherapy effectiveness due to the antioxidant effects of ascorbic acid in the modulation of oxidative stress to promote major cytogenetic damage that is important to tumor regression.