Cancer, one of the most common causes of morbidity and mortality across the world, has always been a main focus of research to devise new treatments modalities and management tools. Researchers have long believed that potentially carcinogenic agents like estrogen and arsenic have well established association with a variety of malignancies, but only at higerh serum concentrations. However, latest research conducted by Texas Tech University have proved otherwise.
Details of the study:
A research team from the Institute of Environmental and Human Health (TIEHH) at Texas Tech identified that estrogen and arsenic in combination (even at low serum concentration) can increase the risk of developing prostate cancer almost twice as much. The results of this discovery have been published in the scientific journal The Prostate.
Kamaleshwar Singh, assistant professor at TIEHH and one of the lead investigators of the study explained the cancer pathogenesis in these words:
“The majority of cancers are caused by environmental influences. Only about 5 to 10 percent of cancers are due to genetic predisposition. Science has looked at these chemicals, such as arsenic, and tested them in a lab to find the amounts that may cause cancer. But that’s just a single chemical in a single test. In the real world, we are getting exposed to many chemicals at once.”
Singh and his associates decided to study two chemicals at the same time after learning about the carcinogenic properties of arsenic in another research paper. Arsenic is abundant in nature (in water sources and wells in most countries of Asia and around the world) and also in cigarette smoke. Similarly, many plastic products, bisphenol A (BPA) and can liners release chemicals in the body that may mimic estrogen in structure and functions. Singh and his doctoral student Justin Treas suggested that the carcinogenic potential of different chemicals may alter when combined with other chemicals (leading to an additive effect even at a sub-toxic/ sub- lethal dose).
The research team exposed human prostate cells to a calculated dose of arsenic and estrogen individually and in combination, once weekly for 6 months. The calculated dose was in accordance with the safe serum concentration as suggested by Environmental Protection Agency.
Singh while explaining the study goals suggested:
Co-exposure was creating a greater impact. That was one of the important findings of our study. The next thing we wanted to know is how these two chemicals are creating a greater effect.”
Researchers identified that the persistent and combined exposure to the two chemicals stopped the expression of MLH1 gene that is associated with initiating the apoptosis cascade after the cell is damaged. The resultant effect is prolonged survival of genetically altered cells that increases the risk of malignant transformation many folds.
Singh and his associates discovered that unlike major carcinogens like benzene and other carbon polymers, estrogen and arsenic do not directly cause DNA damage or genetic mutations; instead these agents stop the expression of certain genes that may culminate in malignancy by a process termed as DNA hypermethylation. Treas suggested:
“With the lower dose not killing the cell, it’s causing damages that go under the cell’s radar. We found when you have two compounds together, lower doses could be more serious problem.”
The results of this remarkable discovery may have an impact on the health regulations governing safe serum concentration of different chemicals, since “safe serum levels” are calculated for most chemicals individually (and not in combination with other chemicals).