The effects of environmental exposure on the DNA-repair capacity in individuals

Exposure to environmental toxicants can lead to dire health consequences if it were not for the defense mechanisms which have evolved to protect us. The hypothesis of my dissertation is that either through an inherited defect or through the pressure of an external mechanism, the DNA repair system can become compromised resulting in genomic instability. The primary interest lies in the effects of environmental toxicant exposure on the DNA repair capacity (DRC) in human populations. We have established a method by which we are able to measure reductions in DRC in lymphocytes of human populations. The following studies validate the usefulness of the Chloramphenicol Acetyl Transferase-Host Cell Reactivation (CAT-HCR) assay as a population monitoring tool. The CAT-HCR assay was tested in three different environmentally exposed populations. The first was a population of workers who were exposed to benzene which is a human leukemogen. In this population we were unable to detect any significant differences between subjects and controls, although intra-individual variations were observed in both groups. The lack of detectable biological effects in these workers is most likely due to the low exposure concentrations of benzene (0.3 ppm). These findings were corroborated by a concurrently conducted hprt mutation assay in which no increase in mutation frequency was observed. A group of petroleum workers exposed to 1,3-butadiene was selected as our second population. A reduction in repair capacity was observed in exposed workers compared with controls. In addition, a reduction in DRC was observed in Exposed-Smokers compared to Exposed-Non-smokers. The overall reduction in DRC indicates contribution by both butadiene and cigarette smoke exposures. The third study population was comprised of cigarette smokers and non-smokers. A reduction in DRC was correlated with age in the pooled population as well as with age in the non-smoking control group. A consistent reduction in DRC was observed in females compared to males. DRC reduction was correlated with increasing pack years. These studies demonstrate the utilization of the CAT-HCR assay as an advanced technique in determining the effects of environmental exposures in human populations.