Investigation of Hepatic Enzyme Systems Ability to Catalyze the DNA Binding of 3-Nitrofluoranthene and 2-Nitrofluoranthene

3-Nitrofluoranthene (3-NFA) and 2-Nitrofluoranthene are environmental pollutants created during combustion processes, proven to be mutagenic in bacterial assays and potentially carcinogenic in mammalian species. The binding of electrophilic metabolites of a nitro-PAH to DNA may lead to mutagenicity and carcinogenicity. This study shows that rat hepatic enzyme systems in S9 are able to catalyze the binding of 3-NFA (labeled with [14]C) and 2-NFA (labeled with [3]H) to calf thymus DNA in vitro. Maximum activity (800-1500 pmole 3-NFA/mg DNA in 1 hour) for 3-NFA occurred in incubations conducted under air and with S9 and NADPH. When NADH was used as a cofactor less activity was obtained (200-500 pmole 3-NFA/mg DNA in 1 hour). The converse held true for 2-NFA as greatest activity occurred under air and with S9 but with NADH (1.1-1.25 pmole 2-NFA/mg DNA in 1 hour). DNA-bound radioactivity was less with NADPH in similar conditions (0.6-0.8 pmole 2-NFA/mg DNA in 1 hour). Addition of other cofactors (FAD and FMN in addition to NAD and NADPH) showed insignificant levels of binding for either isomer. SKF 525A was unable to inhibit DNA binding of both compounds. Addition of glutathione had no effect in incubations with 3-NFA but seem to enhance the DNA binding of 2-NFA. These results indicate the participation of cytochrome P-450 in the oxidative metabolism of 3-NFA and possibly 2-NFA.Master of Science in Public Healt

Risk to human health related to the presence of perfluoroalkyl substances in food

Acknowledgements: The Panel wishes to thank the following for their support provided to this scientific output as Hearing experts: Klaus Abraham, Esben Budtz-Jørgensen, Tony Fletcher, Philippe Grandjean, Hans Mielke and Hans Rumke and EFSA staff members: Davide Arcella, Marco Binaglia, Petra Gergelova, Elena Rovesti and Marijke Schutte. The Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output. The Panel would also like to thank the following authors and co-authors for providing additional information in relation to their respective studies: Berit Granum, Margie M Peden-Adams, Thomas Webster.Peer reviewedPublisher PD