DNA damage induced in mouse tissues by organic wood preserving waste extracts as assayed by 32P-postlabeling |
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Authors: | E Randerath G-D Zhou K C Donnelly S H Safe K Randerath |
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Institution: | (1) Division of Toxicology, Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA, US;(2) Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, TX 77843, USA, US;(3) Department of Veterinary Physiology/Pharmacology, Texas A&M University, College Station, TX 77843, USA, US |
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Abstract: | Numerous wood preserving waste (WPW) sites in the United States pose genotoxic hazards. WPWs consist of complex mixtures
containing toxic, including genotoxic, compounds which are derived from the preservatives coal tar creosote and pentachlorophenol
(PCP) and other polychlorinated aromatics. The genotoxicity of WPW extracts, which has not been tested in mammals, cannot
be evaluated on the basis of data for individual components because of possible compound interactions. Therefore, whole extracts
need to be assayed. 32P-postlabeling represents a powerful tool to determine DNA adduct formation by complex genotoxic mixtures, such as cigarette
smoke, diesel exhaust, and coke oven and foundry emissions in experimental animals and humans. In the present study, a mouse
bioassay was used in combination with 32P-postlabeling to determine DNA adduct formation induced by hexane/acetone extracts of two samples from a WPW site. Female
ICR mice were treated dermally with extract corresponding to 3 mg residue or vehicle control once per day for 2 days and killed
24 h later. Skin, lung, liver, kidney, and heart DNA preparations were assayed by nuclease P1-enhanced postlabeling. Adduct
profiles were tissue-specific and displayed a multitude of non-polar DNA adducts with levels amounting to one adduct in 1.6×106 DNA nucleotides in skin (both extracts) and one adduct in 3.2×107 or 1.2×107 DNA nucleotides in liver (extract 1 or extract 2). Based on their chromatographic properties, these adducts appeared largely
derived from polycyclic aromatic hydrocarbons (PAHs) present in the extracts. One of the major adducts was identified as the
32P-labeled derivative of the reaction product of 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzoa]pyrene (BPDE I) with
N
2 of deoxyguanosine. Total non-polar DNA adduct levels were highest in skin and lung, amounting to 17.4 and 24.0% of the skin
values for extracts 1 and 2, respectively, in lung while the corresponding levels in liver were 5.0 and 12.6%. These results
were in accord with the carcinogenic potencies of PAHs in these organs. Extract 2 induced higher adduct levels in internal
organs, although its PAH concentrations were lower than those of extract 1, i.e. lung, liver, kidney, and heart had 1.4, 2.5,
1.9, and 1.7 times higher total adduct levels and 1.6, 3.3, 1.6, and 1.9 times higher benzoa]pyrene adduct levels. With the
exception of total adducts in lung, the differences between the two extracts were all significant, suggestive of compound
interactions. The benzoa]pyrene adduct levels in the five tissues correlated linearly with total adduct levels and thus represented
a surrogate for the latter. Overall, the results suggest that DNA adducts in mouse tissues, as analyzed by 32P-postlabeling, are suitable biomarkers and dosimeters of the genotoxicity of WPW extracts.
Received: 26 September 1995/Accepted: 7 December 1995 |
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Keywords: | Complex genotoxic mixtures Benzo[a]pyrene DNA adducts |
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