Occupational disease etiology has been difficult to define due to the potentially long latency period between exposure to the harmful chemicals in workplace environment and the clinical manifestation of disease. While we typically monitor the air in the workplace for the presence of hazardous chemicals, we usually monitor for only one of these chemicals at a time and fail to evaluate the synergistic effects of chemical mixtures. Our ability to measure the presence of chemical contaminants in the body using biomonitoring technology continues to progress at a rapid pace, often before we clearly understand the meaning of the results. Our research group has identified a group of over 40 chemicals classified as known or suspected animal neurocarcinogens. By comparing our list to the National Occupational Exposure Survey (NOES) completed by the National Institute for Occupational Safety and Health (NIOSH) we have examined exposure to 24 chemicals from our list that are found in the workplace. We hypothesize that through the use of self-reported work histories an algorithm can be created to quantify cumulative occupational exposures to known or suspected animal neurocarcinogens. We further hypothesize that when cases and controls are compared there may be a statistically significant difference between the cumulative exposure scores of the two groups. Additionally, we hypothesize that hemoglobin adducts of 1, 3-butadiene and acrylamide are valid biomarkers of exposure and can be used to validate the exposure scoring method. Finally, we hypothesize that, by employing a mutagen sensitivity assay, a versatile method for evaluating DNA damage and repair capacity;we will be able to identify an interaction between environmental exposures, as measured by the relative exposure scores, and a genetic susceptibility to the damage caused by certain chemicals. From the results of this proposal, additional hypotheses may be generated to study specific industries and occupations. This research proposal will examine the work histories of study participants who have already participated in a brain cancer case-control study. Participants completed an extensive questionnaire and work history at the time of enrollment in the original study. From the work histories, a relative cumulative exposure score will be generated which evaluates exposure history to the 24 chemicals referenced above. The relative exposure scores will be compared between cases and controls with consideration made for various effect modifiers. Using these relative scores, a sub-set of the study control population will be identified to compare potential workplace exposures in their current occupation with hemoglobin adducts to two common chemicals, acrylamide and 1, 3-butadiene, which act as biomarkers of exposure. Laboratory analysis results will be correlated with the relative scores as a means of validating the scoring method. Finally, a biomarker of susceptibility will be analyzed using a mutagen sensitivity assay for these compounds, and results will be correlated with the relative cumulative exposure scores.
This research focuses on developing and understanding three ways to measure human exposure to two workplace chemicals known to cause brain cancer in animals: occupational history exposure scores, body burden of exposure and biological changes related to human exposure. This will further our understanding of human exposure to these workplace chemicals and the subsequent development of brain cancer. Identifying occupational causes of disease may allow control and prevention strategies to be developed to eliminate or reduce the burden of the disease.
