NTP identifies differential molecular changes in rodent liver tumors
Using a mouse model, scientists at the National Toxicology Program (NTP) have demonstrated that in a type of liver cancer called hepatocellular carcinoma (HCC), methylation and gene expression profiles differ between HCCs that arise spontaneously and those due to chronic exposure to gingko biloba extract (GBE). A commonly used botanical supplement in the U.S., GBE is marketed as an anticancer and antioxidant agent. Previous NTP studies showed that in rodents, exposure to GBE for 2 years results in HCCs, but the mechanisms behind that cancer development are not fully understood.
Epigenetic modifications, such as methylation, can alter gene expression and play an important role in cancer development. The NTP researchers evaluated the global methylation profiles and the corresponding gene expression profiles in mice with HCCs arising either spontaneously or due to GBE exposure. Although these tumors are morphologically indistinguishable, the methylation and gene expression profiles are very different. For example, the researchers were able to validate that the promoter of oncogene c-myc¬ had less methylation in GBE-induced tumors compared to spontaneous tumors. Consistent with the decrease in methylation, c-myc gene expression was upregulated in GBE-induced tumors.
As more chemicals make their way into the environment, studies like this one potentially allow scientists to differentiate between chemically-induced and spontaneous cancers. (ML)
Citation: Kovi RC, Bhusari S, Mav D, Shah RR, Ton TV, Hoenerhoff MJ, Sills RC, Pandiri AR. 2019. Genome-wide promoter DNA methylation profiling of hepatocellular carcinomas arising either spontaneously or due to chronic exposure to Ginkgo biloba extract (GBE) in B6C3F1/N mice. Arch Toxicol; doi:10.1007/s00204-019-02505-7 [Online 5 July 2019].