The genotoxicity of 3-nitrobenzanthrone and the nitropyrene lactones in human lymphoblasts.
Polycyclic aromatic hydrocarbons (PAH) and nitrated polycyclic aromatic compounds (nitro-PAC) have been found to be mutagenic in bacterial and human cells as well as carcinogenic in rodents. In this investigation, the genotoxic effects of 3-nitrobenzanthrone (3NB) and a mixture of nitropyrene lactones (NPLs) were determined using forward mutation assays performed in two human B-lymphoblastoid cell lines, MCL-5 and h1A1v2, which are responsive to the nitro-PAC class of compounds. Mutagenicity of the compounds was determined at the heterozygous tk locus and the hemizygous hprt locus, thus, identifying both large-scale loss of heterozygosity (LOH) events as well as intragenic mutagenic events. Genotoxicity was also determined using the CREST modified micronucleus assay, which detects chromosomal loss and breakage events. Results indicate 3NB is an effective human cell mutagen, significantly inducing mutations at the tk and hprt loci in both cell lines, and inducing micronuclei in the h1A1v2 cell line. The NPL isomers are also mutagenic, inducing mutations at the two loci as well as micronuclei in both cell lines. Because of their mutagenic potencies and their presence in ambient air, further assessments should be made of human exposures to these nitro-PAC and the potential health risks involved.
Phousongphouang
P T
PT
Environmental Toxicology Graduate Program, Air Pollution Research Center, University of California, Riverside, CA 92521, USA.
Grosovsky
A J
AJ
Eastmond
D A
DA
Covarrubias
M
M
Arey
J
J
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000633:toxicity; D002460:Cell Line; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007783:Lactones / Q000633:toxicity*; D019656:Loss of Heterozygosity; D008297:Male; D008558:Melphalan / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011721:Pyrenes / Q000633:toxicity*; D013937:Thymidine Kinase / Q000235:genetics
D001551:Benz(a)Anthracenes; D007783:Lactones; D009153:Mutagens; D011721:Pyrenes; D001564:Benzo(a)pyrene; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase; C117220:3-nitrobenzanthrone; D008558:Melphalan