Work

Ethanol and acetaldehyde mediate folic acid and human papillomavirus-induced proliferation of oral squamous cell carcinoma cells in vitro

Year: 2012

Type: article

Abstract: Background Although great scientific emphasis has been placed upon HPVas the primary cause of cervical cancers and its involvement in carcinogenic progression of other cancers, less attention has been focused on the secondary factors that are associated with progression from subclinical HPV infection to invasive carcinoma. Among the secondary factors that limit virus production and carcinogenic progression is CpG methylation of the HPV genome. Several studies now confirm that CpG site-specific methylation of HPV DNA, mediated in part by folate availability, is sufficient to suppress neoplastic progression. In contrast, demethylation or hypomethylation of HPV-DNA sequences is required for transformation, revealing the importance of preferential DNA methylation at CpG sites in the HPV long control region (LCR) between L1 and E6 HPV genes, in addition to the tumor suppressor sites in p53 exons 248 and 273. Because HPV has the potential to initiate oncogenesis, and also to modulate oral cancer growth and folate plays a central role in mediating the availability of methyl groups for CpG-specific DNA methylation (modulating both p53 and HPV mRNA expression) – an investigation of these inter-connected and inter-related mechanisms in oral cancers must be undertaken. In addition, ethanol and acetaldehyde may also play critical roles in determining folate availability, and are primary risk factors for the development of oral cancers, which makes the evaluation of these interconnected metabolic pathways critically important. Materials and methods Using a comprehensive series of integrated in vitro assays, including proliferation, viability and mRNA analysis using RT-PCR, distinct effects of ethanol and acetaldehyde administration were observed in the oral cancer cell lines, CAL27, SCC15 and SCC25. In addition, the growth modulating effects of HPV infection and FA supplementation were also examined.

Source: BMC Proceedings

DOI: 10.1186/1753-6561-6-s3-p64