A new study by researchers from the University of Birmingham suggests that environmental cancer-causing agents may be used to help understand effects of exposure in addition to helping predict the individuals who may be more susceptible to developing cancer.
Every individual has been exposed to low levels of radiation or substances that promote cancer development, commonly known as carcinogens. Benzopyrene, which is a widely used chemical pollutant, is found in barbequed fish and meat, exhaust fumes and wood-burning stoves. The pollutant has BPDE, which is an active ingredient that forms DNA adducts. These are damaged DNA that promote mutations that give rise to cancer.
While researchers still don’t fully understood some pathways, models that demonstrate how BPDE leads to these mutations have been developed. Scientists believe that the mutation occurs through a process called translesion synthesis, which happened when cells replicate damaged DNA. However, research has also revealed that another process known as homologous recombination is also involved in the process. This process copies other undamaged parts of the genome.
The study researchers used BPDE to treat human cell lines before they used molecular biology methods such as microscopy to characterize the homologous recombination pathway in depth. The findings have shown that homologous recombination (HR) can be activated even when there isn’t any collapsed or stalled replication forks. Instead, researchers say that HR is activated in the DNA’s single-stranded gaps created by PrimPol’s re-priming activity. PrimPol is a protein encoded by the gene, PRIMPOL, which is found in humans.
The results also provide new insights that show that at bulky DNA adducts, HR products that have been traditionally linked to replication fork collapse and exchanges between sister chromatids are connected to post-replicative gap repair. Moreover, it was found that PrimPol produces these post-replicative gaps, which explains PrimPol’s function in DNA damage tolerance.
Eva Petermann, MD, the study’s corresponding author from the Institute of Cancer and Genomic Sciences, University of Birmingham, states that the study demonstrated how cells were affected when exposed to benzopyrene. This is important in helping researchers better understand cancer development in general and the environmental causes of cancer. Understanding this mechanism may help scientists better detect and predict the detrimental effects of pollution while also allowing them to better interpret cancer genomics.
As research progresses, Petermann explains that it will be important to look into the effect of such gene variants on homologous recombination at ssDNA gaps. She adds that a variant of the PRIMPOL gene may even have the potential to predict which individuals are more sensitive to carcinogen exposure.
Cancer takes a huge toll on society and many companies are doing their best to improve the delivery and effectiveness of cancer treatment. One such company is Predictive Oncology (NASDAQ: POAI). POAI specializes in improving patient treatment outcomes by combining the power of data and AI to personalize cancer treatment.
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