Event Title

Comparative metabolism of environmentally occurring phenanthro[3,4-b]thiophene and benzo[c]phenanthrene

Start Date

31-10-2013 11:00 AM

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Comparative metabolism of environmentally occurring phenanthro[3,4-b]thiophene and benzo[c]phenanthrene Presenters: Subodh Kumar, Jaquan Williams, and Jagat J. Mukherjee Polycyclic aromatic hydrocarbons (PAHs) and their sulfur-heterocyclic analogs (thia-PAHs) are commonly occurring persistent environmental contaminants formed by incomplete combustion of organic matter. A number of thia-PAHs have shown significant mutagenic and carcinogenic activities. As noted with PAHs, these chemical contaminants also require metabolic activation in order to exhibit their mutagenic and carcinogenic effects. In the present study, a comparative metabolism of highly mutagenic phenanthro[3,4-b]thiophene (P[3,4-b]T) and its weakly mutagenic carbon analogue, benzo[c]phenanthrene (B[c]P), were investigated. Metabolism studies were conducted using liver microsomes from induced rats, un-induced rats, as well as lung microsomes from smokers and non-smokers. While all of the microsomes metabolized B[c]P to ring oxidation products (predominantly K-region B[c]P 5,6-diol), P[3,4-b]T is metabolized to both ring oxidation products (predominantly benzo-ring P[3,4-b]T 8,9-diol) and S-oxidation products (predominantly P[3,4-b]T sulfone). P[3,4-b]T is a more potent mutagen than its homocyclic analog B[c]P. Previous studies have shown that, like many carcinogenic PAHs, B[c]P is metabolically activated to B[c]P 3,4-diol to produce mutagenic and carcinogenic effects. However, our recent studies with P[3,4-b]T, have shown that, in contrast to P[3,4-b]T 8,9-diol, a corresponding sulfur analog of B[c]P 3,4-diol, sulfone exhibited significantly higher mutagenic activity compared to P[3,4-b]T. This earlier finding along with our present study, lends support to our hypothesis that unlike B[c]P, P[3,4-b]T exhibits its mutagenic and possibly carcinogenic activity predominantly via sulfoxidation pathway.

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Oct 31st, 11:00 AM

Comparative metabolism of environmentally occurring phenanthro[3,4-b]thiophene and benzo[c]phenanthrene

Comparative metabolism of environmentally occurring phenanthro[3,4-b]thiophene and benzo[c]phenanthrene Presenters: Subodh Kumar, Jaquan Williams, and Jagat J. Mukherjee Polycyclic aromatic hydrocarbons (PAHs) and their sulfur-heterocyclic analogs (thia-PAHs) are commonly occurring persistent environmental contaminants formed by incomplete combustion of organic matter. A number of thia-PAHs have shown significant mutagenic and carcinogenic activities. As noted with PAHs, these chemical contaminants also require metabolic activation in order to exhibit their mutagenic and carcinogenic effects. In the present study, a comparative metabolism of highly mutagenic phenanthro[3,4-b]thiophene (P[3,4-b]T) and its weakly mutagenic carbon analogue, benzo[c]phenanthrene (B[c]P), were investigated. Metabolism studies were conducted using liver microsomes from induced rats, un-induced rats, as well as lung microsomes from smokers and non-smokers. While all of the microsomes metabolized B[c]P to ring oxidation products (predominantly K-region B[c]P 5,6-diol), P[3,4-b]T is metabolized to both ring oxidation products (predominantly benzo-ring P[3,4-b]T 8,9-diol) and S-oxidation products (predominantly P[3,4-b]T sulfone). P[3,4-b]T is a more potent mutagen than its homocyclic analog B[c]P. Previous studies have shown that, like many carcinogenic PAHs, B[c]P is metabolically activated to B[c]P 3,4-diol to produce mutagenic and carcinogenic effects. However, our recent studies with P[3,4-b]T, have shown that, in contrast to P[3,4-b]T 8,9-diol, a corresponding sulfur analog of B[c]P 3,4-diol, sulfone exhibited significantly higher mutagenic activity compared to P[3,4-b]T. This earlier finding along with our present study, lends support to our hypothesis that unlike B[c]P, P[3,4-b]T exhibits its mutagenic and possibly carcinogenic activity predominantly via sulfoxidation pathway.