You are here:
THE APPLICATION OF COMPUTATIONAL MOLECULAR METHODS TO UNDERSTAND THE HEALTH EFFECTS OF ENVIRONMENTAL CHEMICALS-POLYCYCLIC AROMATIC HYDROCARBONS
Citation:
Rabinowitz, J. R., S. B. Little, AND K. W. Brown. THE APPLICATION OF COMPUTATIONAL MOLECULAR METHODS TO UNDERSTAND THE HEALTH EFFECTS OF ENVIRONMENTAL CHEMICALS-POLYCYCLIC AROMATIC HYDROCARBONS. Presented at EURESCO Conference, Computational Biophysics, San Feliu de Guixols, Spain, 9/7-12/2002.
Description:
In evaluating the risk posed by chemicals introduced into the environment, information
about their molecular mechanism of action provides a basis for extrapolating from the
laboratory to the environment. Polycyclic aromatic hydrocarbons (PAH) are a large class
of anthropogenic chemicals found in a number of environmental circumstances. Some
class members are potent mutagens and animal carcinogens while other class members
show little similar activity after considerable testing. Benzo[a]pyrene (BaP) is a class
member that has been identified as a carcinogen. The features of its structure that might
confer this activity were identified and studied by a number of different methods. A
metabolite, the bay region diol epoxide, was identified as the ultimate carcinogen and its
structure and reactivity studied by molecular modeling methods. When considering a
series of bay region diolepoxides, it was found that molecules with a crowded bay region
have a different pattern of interaction with DNA than molecules with a simple bay
region. The PAHs with a crowded bay region were often found to be more potent
mutagens and carcinogens. These PAHs and their diol epoxides were also shown to be
nonplanar. The relationship between bay region crowding, nonplanarity and reactivity
will be discussed. The interaction of PAHs and their metabolites with the estrogen
receptor will also be discussed in consideration of possible mechanisms of action for
additional environmental effects.
(This work does not necessarily reflect EPA policy)