Probabilistic health risk assessment for exposures to estuary sediments and biota contaminated with polychlorinated biphenyls, polychlorinated terphenyls and other toxic substances.

A Latin Hypercube probabilistic risk assessment methodology was employed in the assessment of health risks associated with exposures to contaminated sediment and biota in an estuary in the Tidewater region of Virginia. The primary contaminants were polychlorinated biphenyls (PCBs), polychlorinated terphenyls (PCTs), polynuclear aromatic hydrocarbons (PAHs), and metals released into the estuary from a storm sewer system. The exposure pathways associated with the highest contaminant intake and risks were dermal contact with contaminated sediment and ingestion of contaminated aquatic and terrestrial biota from the contaminated area. As expected, all of the output probability distributions of risk were highly skewed, and the ratios of the expected value (mean) to median risk estimates ranged from 1.4 to 14.8 for the various exposed populations. The 99th percentile risk estimates were as much as two orders of magnitude above the mean risk estimates. For the sediment exposure pathways, the stability of the median risk estimates was found to be much greater than the stability of the expected value risk estimates. The interrun variability in the median risk estimate was found to be +/- 1.9% at 3000 iterations. The interrun stability of the mean risk estimates was found to be approximately equal to that of the 95th percentile estimates at any number of iterations. The variation in neither contaminant concentrations nor any other single input variable contributed disproportionately to the overall simulation variance. The inclusion or exclusion of spatial correlations among contaminant concentrations in the simulation model did not significantly effect either the magnitude or the variance of the simulation risk estimates for sediment exposures.

Repair of aflatoxin B1 DNA adducts by the UvrABC endonuclease of Escherichia coli.

The repair by UvrABC endonuclease of two major adducts formed by aflatoxin B1 in DNA was found to be similar. Aflatoxin epoxide was used to generate the aflatoxin B1.N7-guanine adduct which can convert to aflatoxin B1-formamidopyrimidine adduct. The reaction of the aflatoxin B1 epoxide with DNA follows pseudo-first order kinetics. The DNA sequence-specific relative reactivity of the epoxide is the same as previously observed for aflatoxin B1 activated by liver microsomes, therefore strongly reinforcing the notion that aflatoxin B1 reacts with DNA through the epoxide intermediate. For the majority of lesion sites, a high affinity protein-DNA complex was formed from the UvrA and the UvrB proteins with similar efficiency to both adducts, and to pyrimidine dimers, and then nicks the DNA when UvrC was added. The two incisions are at the eighth phosphodiester moiety 5' and the sixth phosphodiester moiety 3' of a modified guanine nucleotide. Both incisions appeared to be concerted. For some sites, the DNA sequence can alter the relative incision efficiency up to 15-fold. However, the majority of these AFB1 lesion structures in most DNA sequences are similar with respect to recognition by this nucleotide excision repair enzyme. Therefore the observation that the aflatoxin B1.N7-guanine lesion is removed rapidly, while the aflatoxin B1-formamidopyrimidine lesion persists in the mammalian cell may have other mechanistic explanations.

Methods for the isolation and detection of etheno adducts in nucleotide pools in vivo following exposure to ethyl carbamate.

Cellular extraction and high-performance liquid chromatographic methods were developed for the isolation of etheno adducts from nucleotide pools formed in vivo following exposure to the chemical carcinogen ethyl carbamate. These techniques were employed to detect etheno adduct formation using BDF1 mice and rainbow trout (Salmo gairdneri) as test species following inter-peritoneal injection of the chemical. Ethenoadenine was detected in splenocyte nucleotide pools of mice after acute (24 h) exposure and chronic (two weeks) exposure. Several etheno adducts (i.e. ethenoadenine, etheno-AMP, etheno-ADP and etheno-ATP) were also detected in total spleen cell nucleotide pools of trout following acute ethyl carbamate exposure.

Self-chemical ionization Fourier transform ion cyclotron resonance mass spectrometry: identification and characterization of modified and unmodified bases and nucleosides.

Self-chemical ionization Fourier transform ion cyclotron resonance (FT-ICR) mass spectra are reported for bases, nucleosides, and alkylated and exocyclic adducts of bases and nucleosides. The technique always produces a protonated molecular ion and in the majority of cases this is a single, intense peak. Analysis of a base mixture and a nucleoside mixture demonstrates the technique as an excellent method to identify the constituent compounds qualitatively. The high resolution capabilities and tandem mass spectrometric techniques (msn) in FT-ICR are discussed with respect to developing the technique as a future method to identify and characterize nucleic acid constituents, specifically adducts.