Impact of environmental regulations on lead concentrations in Texas ambient air and water: 1970--1990

In the last two decades, the significance of lead has been addressed in a number of environmental regulations at the national and state levels. This project investigated the environmental regulations (Clean Air Act and Amendments, 1970-1990 and Clean Water Act of 1977) and their cumulative effects on lead in ambient air and water in the state of Texas. For this purpose, historical records from the Texas Water Development Board, Texas Natural Resources Conservation Commission, and the United States Geological Survey have been assembled and analyzed for temporal and spatial trends. These trends might correspond to the phase out of lead in gasoline and other regulations.^ This study concluded that there is a significant correlation (p $\leq$.001) between environmental regulations of lead in gasoline and the concentration of lead in ambient air. Lead concentrations in ambient air have been reduced by over 90 percent in the past twenty years. An overall significant difference (p $\leq$.001) was found in mean (94, 15 respectively) lead concentrations in surface water between two time periods, one at the beginning of the twenty year period and one at the end of the study period. There has been an overall reduction of lead concentrations in surface water in Texas of approximately 84 percent. However, this reduction cannot be statistically associated with any one regulation. Groundwater data could not be analyzed for lead concentrations because of limitations of reporting data as "less than". Approximately two percent of the groundwater data was analyzed by Oneway ANOVA and no significant difference was found between the means (18, 19 respectively) of two time periods, 1977-1979 and 1988-1990. This data is consistent with the regulations having a contributory affect on declining concentrations, but other factors cannot be ruled out as having added to these declines. This study can also serve as a starting point for a more in-depth study of environmental regulations and their impact on the environment. ^

EVIDENCE OF HUMAN ENDOGENOUS RETROVIRUS K INVOLVEMENT IN HUMAN CANCER

Many lines of clinical and experimental evidence indicate a viral role in carcinogenesis (1-6). Our access to patient plasma, serum, and tissue samples from invasive breast cancer (N=19), ductal carcinoma in situ (N=13), malignant ovarian cancer (N=12), and benign ovarian tumors (N=9), via IRB-approved and informed consent protocols through M.D. Anderson Cancer Center, as well as normal donor plasmas purchased from Gulf Coast Regional Blood Center (N=6), has allowed us to survey primary patient blood and tissue samples, healthy donor blood from the general population, as well as commercially available human cell lines for the presence of human endogenous retrovirus K (HERV-K) Env viral RNA (vRNA), protein, and viral particles. We hypothesize that HERV-K proteins are tumor-associated antigens and as such can be profiled and targeted in patients for diagnostic and therapeutic purposes. To test this hypothesis, we employed isopycnic ultracentrifugation, a microplate-based reverse transcriptase enzyme activity assay, reverse transcription – polymerase chain reaction (RT-PCR), cDNA sequencing, SDS-PAGE and western blotting, immunofluorescent staining, confocal microscopy, and transmission electron microscopy to evaluate v HERV-K activation in cancer. Data from large numbers of patients tested by reverse transcriptase activity assay were analyzed statistically by t-test to determine the potential use of this assay as a diagnostic tool for cancer. Significant reverse transcriptase enzyme activity was detected in 75% of ovarian cancer patients, 53.8% of ductal carcinoma in situ patient, and 42.1% of invasive breast cancer patient samples. Only 11.1% of benign ovarian patient and 16.7% of normal donor samples tested positive. HERV-K Env vRNA, or Env SU were detected in the majority of cancer types screened, as demonstrated by the results shown herein, and were largely absent in normal controls. These findings support our hypothesis that the presence of HERV-K in patient blood circulation is an indicator of cancer or pre-malignancy in vivo, that the presence of HERV-K Env on tumor cell surfaces is indicative of malignant phenotype, and that HERV-K Env is a tumor-associated antigen useful not only as a diagnostic screening tool to predict patient disease status, but also as an exploitable therapeutic target for various novel antibody-based immunotherapies.