부산대학교 도서관

Oxidized methylcytidines 5-hydroxymethyl-2′deoxycytidine (5hmdC) and 5-formy-2′deoxycytidine (5fdC) are deaminated by cytidine deaminase (CDA) into genome-toxic variants of uridine, triggering DNA damage and cell death. These compounds are promising chemotherapeutic agents for cancer cells that are resistant to pyrimidine derivative drugs, such as decitabine and cytarabine, which are inactivated by CDA. In our study, we found that cancer cells infected with mycoplasma exhibited a markedly increased sensitivity to 5hmdC and 5fdC, which was independent of CDA expression of cancer cells. In vitro biochemical assay showed that the homologous CDA protein from mycoplasma was capable of deaminating 5hmdC and 5fdC into their uridine form. Moreover, mycoplasma infection increased the sensitivity of cancer cells to 5hmdC and 5fdC, whereas administration of Tetrahydrouridine (THU) attenuated this effect, suggesting that mycoplasma CDA confers a similar effect as human CDA. As mycoplasma infection occurs in many primary tumors, our findings suggest that intratumoral microbes could enhance the tumor-killing effect and expand the utility of oxidized methylcytidines in cancer treatment. [Display omitted] • Tumor killing effect of 5hmdC and 5fdC is enhanced by mycoplasma infection. • Mycoplasma cytidine deaminase deaminates 5hmdC and 5fdC into cytotoxic agents. • Intratumoral microbes may expand the utility of 5hmdC and 5fdC in cancer treatment. [ABSTRACT FROM AUTHOR]