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. 2005 Apr;2(1):114-22.
doi: 10.3390/ijerph2005010114.

Photochemical reaction of 7,12-dimethylbenz[a]anthracene (DMBA) and formation of DNA covalent adducts

Hongtao Yu  1 , Jian Yan, Yuguo Jiao, Peter P Fu
Affiliations

Photochemical reaction of 7,12-dimethylbenz[a]anthracene (DMBA) and formation of DNA covalent adducts

Hongtao Yu et al. Int J Environ Res Public Health. 2005 Apr.

Abstract

DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

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Figures

Figure 1
Figure 1
HPLC profiles of photoproducts of DMBA after irradiation with UVA light (2.6 J/cm2/min) in ethanol for (A) 40 min; (B) 90 min; (C) 360 min.
Figure 2
Figure 2
Identification of some of the photoproducts of DMBA in ethanol after 360 min of irradiation using UVA light (2.6 J/cm2/min).
Figure 3
Figure 3
Mass spectrum profiles of purified P5 (A) and P8 (B) of DMBA photoproducts.
Figure 4
Figure 4
1H-NMR spectra of purified P5 (A) and P8 (B) of DMBA photoproducts.
Figure 5
Figure 5
HPLC and UV spectrum profiles of 7-hydroxymethyl-12-methylbenz[a]anthracene standard (A), purified P6 from DMBA photoproducts (B); benz[a]anthracen-7,12-dione standard (C), and purified P9 from DMBA photoproducts (D).
Figure 6
Figure 6
Time course of photodecomposition of DMBA and formation and photodecomposition of the identified DMBA photodecomposition products.
Figure 7
Figure 7
Autoradiogram of 32P-postlabeled nuclease P1-treated DNA from photo-irradiation in the presence of (A) DMBA, (B) blank, (C) 7-HOCH2-12-MBA, (D) 12-HOCH2-7-MBA, (E) 7-CHO-12-MBA, and (F) 12-CHO-7-MBA in THF and calf thymus DNA by UVA light at a total dose of 14 J/cm2.
Figure 8
Figure 8
Autoradiogram of 32P-postlabeled nuclease P1-treated calf thymus DNA from (A) photo-irradiation of the DNA in the presence of DMBA by UVA light (14 J/cm2) and (B) the metabolite mixture from metabolism of DMBA by rat liver microsomes in the presence of calf thymus DNA.
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