Structure, Function, and Carcinogenicity of Oxidized Metabolites of Methylated and non-Methylated Polynuclear Hydrocarbons

Date: 
10/07/2016 - 4:00pm to 4:50pm
Location: 
CP-114
Speaker(s) / Presenter(s): 
James Flesher

Professor Emeritus Jame Flesher from the University of Kentucky's Deparetment of Pharmacology will present his seminar titled Structure, Function, and Carcinogenicity of Oxidized Metabolites of Methylated and non-Methylated Polynuclear Hydrocarbons.

Abstract:
The Unified Theory of PAH Carcinogenicity accommodates the activities of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) and states that substitution of methyl groups on meso-methyl substituted PAHs with hydroxy, acetoxy, chloride, bromide or sulfuric acid ester groups imparts potent cancer producing properties. It incorporates specific predictions from past researchers on the mechanism of carcinogenesis by methyl-substituted hydrocarbons, including (1) requirement for metabolism to an ArCH2X type structure where X is a good leaving group and (2) biological substitution of a meso-methyl group at the most reactive center in non-methylated hydrocarbons. The Theory incorporates strong inferences of Fieser: (1) The mechanism of carcinogenesis involves a specific metabolic substitution of a hydrocarbon at its most reactive center and (2) Metabolic elimination of a carcinogen is a detoxifying process competitive with that of carcinogenesis and occurring by a different mechanism. According to this outlook, chemical or biochemical substitution of a methyl group at the reactive meso-position of non-methylated hydrocarbons is the first step in the mechanism of carcinogenesis for most, if not all, PAHs and the most potent metabolites of PAHs are to be found among the meso methyl-substituted hydrocarbons. Some PAHs and their known or potential metabolites and closely related compounds have been tested in rats for production of sarcomas at the site of subcutaneous injection and the results strongly support the specific predictions of the Unified Theory.

 

Type of Event (for grouping events):
X
Enter your linkblue username.
Enter your linkblue password.
Secure Login

This login is SSL protected

Loading