Analysis of the Pathways to Colorectal Carcinogenesis by Bisphenol A-
Dr Wael Abdel-Rahman Hassan, MD, PhD
Various types of studies support the evidence that environmental toxins and carcinogens including external hormone-like materials that contaminate our foods and drinks play an important role in the development of breast and colon cancer. It is also well established that cancers develop as a result of molecular changes leading to stepwise accumulation of mutations and or epimutations within the cell. In particular, accumulating body of evidence indicates that endocrine disrupting chemicals that could mimics estrogen action such as bisphenol A (BPA) can act as carcinogens and enhance susceptibility to tumorigenesis within the female genital tract. Although, there is good evidence to implicate some ingested food carcinogens in the pathogenesis of colorectal cancers, the effects of ingested BPA in colorectal carcinogenesis as well as tumor progression and metastasis was not thoroughly addressed at the molecular level so far. In the current work we have acquired and maintained distinct patterns of normal/immortalized colon epithelial cells or less aggressive colon cancer cells in the lab and exposed them to BPA or related toxins; and then analyzed their behavior and various cellular parameters after exposure for different periods. The exposure to toxic agents was up to two month which is considered long compared to the standard few days period used in many previous experiments in this field.
Substantial progress was made so far and we have generated interesting alarming findings. Most of the tested agents prolong cell viability and make the cells resistant to killing by standard chemotherapeutics. This observation was detected by multiple techniques and observed both in normal and malignant cells. This effect was mainly due to abrogation of apoptosis through both intrinsic and extrinsic pathways. Toxic agents also induce DNA damage as detected mainly by over-expression of some established markers (pH2AX, pCHK1, pCHK2, pP53). There have been some changes in the cellular abilities to form colonies but this is still ongoing experiment as well as the methylation analyses for which DNA preparation was completed. Overall, the available data supply good foundation to understanding and prevention of environmental carcinogenesis.
Dr Wael M Abdel-Rahman (Hassan); MBBCH, MSc (Pathology), PhD (Molecular Pathology) is the coordinator of the MSc/PhD program in Molecular Medicine, College of Medicine, University of Sharjah; a member of the University Postgraduate Studies Council and the chair of the CoH Research Committee. He served the University of Sharjah and the scientific community at many other committees, and boards.
His PhD work was carried out at Edinburgh and Cambridge Universities, UK, with a focus on molecular genetics of colorectal cancer, during which he identified a novel molecular cytogenetic profile in colorectal cancers. At the Department of Medical Genetics, University of Helsinki, Finland (2002-2007, then as an honorary Professor till present), he directed his efforts to the study and diagnosis of familial cancers and contributed to seminal discoveries in this field. Currently, his research at the University of Sharjah aims to understand the environmental causes of cancers and how this could be related to resistance of cancer cells to therapy. He has published a series of landmark research articles and critical reviews on the genetics of colorectal, endometrial and other cancers in leading international journals including Gastroenterology, Gut, Cancer Research, Oncogene, and Journal of Clinical Oncology.