On the other hand, in this study we found a significant increase in DNA damage such as DNA strands breaks after exposure to CSC of lung cells expressing HPV-16 E6 and E7 oncogenes. Both E6 and E7 were able to induce a significant DNA damage in lung cells exposed to 10 ��g/mL CSC, however the effect of E7 was significantly higher. This is the first study reporting this effect in lung epithelial cells and suggesting collaboration for carcinogenesis. Previously, it was reported that E6 and E7 were able to increase oxidative DNA damage induced by CSC in cervical cancer cells. Moreover, it has been reported that both E6 and E7 independently are able to induce DNA damage in different cells. In fact, it was found that HPV-16 E6 disrupts the fidelity of DSB repair contributing to genetic instability in HPV associated tumors. In addition, recently it was reported that E6_ increases ROS levels and DNA damage in host cells. On the other hand, Park JW et al suggested that E7 is associated to DNA damage at least in part through the inactivation of pocket proteins. Previous studies used benzo pyrene to show an interaction with HPV in cervical keratinocytes. In this respect, functional studies using organotypic ��raft�� cultures, have demonstrated that benzo pyrene, depending on its concentration, is able to increase the number of virions and genomes of HPV. While high concentrations of benzo pyrene, favored virions synthesis, low concentrations of benzo pyrene amplified the number of HPV genomes. The authors suggested that cyclin dependent kinase 1, activated after incubation with benzo pyrene may be involved in virion maturation; a mechanism used by diverse viruses in morphogenesis. In addition, the same authors suggested that an increased CDK1 activity could increase the viral persistence into the cells. In addition, it has been reported that benzo pyrene increases the HPV E7 Doxorubicin expression in a model of cervical raft cultures, and this overexpression is inhibited by curcumin, a potential chemopreventive agent. Because curcumin targets NF-��B and AP1 molecules, the authors suggested that a direct action of these molecules is involved in benzo pyrene-induced E7 expression. On the other hand, it was proposed that high-risk HPV E6 oncoprotein is able to activate serine/threonine-protein kinase CHK1 by phosphorylation at S345 in fibroblasts, in presence of SU5416 genotoxic agents such as benzo pyrene. As CHK1 is a kinase involved in G2 checkpoint, these findings suggested a mechanism for a synergism between a genotoxic agent and high-risk HPV E6 expression. On the other hand, it was suggested that CHK2 is activated by phosphorylation by high-risk HPV for inducing the DNA damage response under differentiation conditions.