Investigation by mass spectrometry and 32P post-labelling of DNA adducts formation from 1,2-naphthoquinone, an oxydated metabolite of naphthalene

Naphthalene is the simplest representative of polycyclic aromatic hydrocarbons (PAHs). It is detected as major pollutant in the different compartments of the environment. This compound is considered by the international agency for research on cancer (IARC), the specialized cancer agency of the World Health Organisation (WHO), as a possible carcinogenic (group 2B) since 2002, mainly based on studies on chronic inhalation in rodent by the national toxicology program of the U.S. department of health and human services. In humans, its main metabolites correspond to derivatives substituted in position and 1 and 2 as 1,2-naphthoquinone (1,2-NphQ). Based on previous studies, 1,2-NphQ is supposed to react with DNA to form mostly depurinating adducts, a possible initiating step of carcinogenicity. To confirm this potentiality, adducts were synthetized by the reaction of 1,2-NphQ with 20-deoxyguanosine (20-dG) in N,N-dimethylformamide (DMF), water and calf thymus DNA. 20-dG adducts were analyzed by 32P postlabelling, HPLC with ultra-violet detection and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). We found stable DNA adducts detected in DNA. We proposed a formation mechanism by a 1,4-Michael addition with 20-dG. Adducts with 20-deoxyxanthosine are formed after a spontaneous deamination of 20-dG. These adducts are good candidates as biomarkers allowing evaluation of exposure to naphthalene and its derivatives in the development of pathologies such as cancer. (C) 2020 Elsevier Ltd. All rights reserved.

Automated summary

Naphthalene, a simple representative of polycyclic aromatic hydrocarbons, is considered a possible carcinogen. Its main metabolite 1,2-NphQ may initiate carcinogenicity by reacting with DNA. Stable DNA adducts were found, serving as biomarkers for evaluating exposure to naphthalene and its derivatives in disease development like cancer.