DNA adduct formation and oxidative stress from the carcinogenic urban air pollutant 3-nitrobenzanthrone and its isomer 2-nitrobenzanthrone, in vitro and in vivo.
The carcinogenic vehicle emission product 3-nitrobenzanthrone (3-NBA) is known to rearrange in the atmosphere to the isomer 2-nitrobenzanthrone (2-NBA), which exists in 70-fold higher concentration in ambient air. The genotoxicity of 2-NBA and 3-NBA was studied both in vitro (human cell lines A549 and HepG2) and in vivo (F344 female rats intra-tracheally administered 5 mg/kg body weight of 3-NBA) models, using the (32)P-HPLC and the single-cell gel electrophoresis (Comet assay) methods. In vitro, also the parent compound benzanthrone (BA) and the metabolite 3-aminobenzanthrone (3-ABA) were evaluated. 3-NBA gave highest levels of DNA adducts in the two cell lines, but significantly higher in HepG2 (relative adduct level approximately 500 adducts/10(8) normal nucleotides), whereas 2-NBA formed about one-third and one-twentieth of the DNA adduct amount in A549 and HepG2 cells, respectively. 3-ABA formed only minute amounts of DNA adducts and only in the A549 cells, whereas BA did not give rise to any detectable levels. The DNA adduct patterns from 3-NBA were similar between the two model systems, but differed somewhat for 2-NBA. The oxidative stress induced by BA was almost as high as what was observed for 3-NBA and 3-ABA in both cell lines, and 2-NBA induced lowest level of oxidative stress. The oxidative stress and DNA adduct level, in whole blood, was significantly increased by 3-NBA but not by 2-NBA. However, 2-NBA showed similar toxicity to 3-NBA, with respect to DNA adduct formation in vivo, hence it is important to further study 2-NBA as a potential contributor to health risk. While DNA adduct level in the 3-NBA-exposed animals reached a peak around 1 and 2 days after instillation, 2-NBA-treated animals showed a tendency towards a continuing increase at the end of the study.
Nagy
Eszter
E
Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 57 Huddinge, Stockholm, Sweden.
Adachi
Shuichi
S
Takamura-Enya
Takeji
T
Zeisig
Magnus
M
Möller
Lennart
L
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000737:chemistry* / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects; D005260:Female; D006801:Humans; D007536:Isomerism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000393:Air Pollutants; D001551:Benz(a)Anthracenes; D002273:Carcinogens; D018736:DNA Adducts; C117220:3-nitrobenzanthrone