Superfund Research Program
Detection, Prioritization and Detoxification of Developmental Toxicants Associated with Chemical Wastes
Project Leader: Timothy D. Phillips
Grant Number: P42ES004917
Funding Period: 1995 - 2000
- Project Summary
Final Progress Reports
Studies have been completed and published comparing the genotoxicity of chemically characterized environmental PAH mixtures. A total of three extracts were selected from sediment samples collected from a lake adjacent to an abandoned coal gasification site. Extract 1 (E1) was collected closest to the shore, E2 at an intermediate distance, and E3 furthest from the shore. Samples were evaluated for their ability to elicit point mutations in Salmonella and DNA adducts in vitro without metabolic activation or in vivo. Adducts were analyzed by nuclease P1 enhanced 32P-postlabeling. In vivo assays were conducted following extract application to mouse skin. For overall assessment, toxicity indices were calculated by combining results of the individual assays including chemical analysis. With some exceptions, the assays indicated decreasing levels of contamination and genotoxicity with increasing distance from the source of contamination. One exception was that sample E2 induced the greatest genotoxic response in skin in vivo as well as in Salmonella. Among internal organs, all three extracts induced the highest adduct levels in the lung, and the values in this organ correlated well with chemical analysis expressed as benzo(a)pyrene equivalents. The toxicity index also reflected the chemical composition of the extracts. In preliminary experiments, similar methodology (PAH analysis, in vivo 32P-postlabeling, and Salmonella test) was applied to three contaminated soils taken near an oil production facility in Baku, Azerbaijan. Again, in vivo 32P-postlabeling data tended to reflect the PAH composition of the extracts. In view of the previous observation that, in addition to producing carcinogen adducts, exposure to complex environmental mixtures of genotoxicants affects levels of endogenous DNA adducts, researchers have continued studies of environmental factors involved in the formation of endogenous adducts. Both endogenous adducts formed by unknown mechanisms (type I I-compounds) and bulky DNA lesions elicited by oxidative stress (type II I-compounds) were investigated. The involvement of toxic metals in the in vivo formation of oxidative lesions has been suggested. The current state of knowledge of I-compounds has been recently reviewed.