Extensions of the adaptive response are the toxic responses elicited by Ahr activation. Toxicity results from two different ways of Ahr signaling. The first is a side effect of the adaptive response in which the induction of metabolizing enzymes results in the production of toxic metabolites. For example, the polycyclic aromatic hydrocarbon benzo[ a ]pyrene (BaP), a ligand for Ahr, induces its own metabolism and bioactivation to a toxic metabolite via the induction of CYP1A1 and CYP1B1 in several tissues.  The second approach to toxicity is the result of aberrant changes in global gene transcription beyond those observed in the "Ahr gene battery." These global changes in gene expression lead to adverse changes in cellular processes and function.  Microarray analysis has proved most beneficial in understanding and characterizing this response.    
Dr. Ashworth received his . in biochemistry from the University College London in 1984. After his postdoctoral fellowship at the University College London and The Institute of Cancer Research (ICR), he joined the faculty of ICR, becoming the first Director of the Breakthrough Breast Cancer Research Center in 1999 and ICR’s Chief Executive Officer in 2011. In 2015, Dr. Ashworth joined the University of California San Francisco (UCSF) as President of the UCSF Helen Diller Family Comprehensive Cancer Center and Senior Vice President for cancer clinical services in UCSF Health. He is a Professor of Medicine in the Division of Hematology/Oncology, Department of Medicine, and E. Dixon Heise Distinguished Professor in Oncology. He is the co-director of UCSF’s Center for BRCA Research, which opened in 2016, and inaugural chair of the University of California Cancer Consortium that launched in September 2017. Dr. Ashworth’s pioneering research has shed light on some of the genetic changes that drive many inherited breast cancers, stimulated a new a field of research, and advanced the development of a novel class of “synthetic lethal” cancer therapies. His continuous focus on translating his laboratory finding to the clinic has paved the way for more personalized treatment options for patients with BRCA mutations, and will have a lasting impact for years to come.