The identification of mutagenic compounds is an important societal goal. short-term tests that employ mammalian enzymes (generally mixed-function oxidases from rat liver) to provide metabolic activation of premutagens to ultimate mutagens have been developed for this purpose. it is now clear that… More

Assays that employ mammalian enzymes (generally mixed- function oxidases from rat liver) to provide metabolic activation of premutagens to ultimate mutagens have been developed and are widely used to identify mutagenic compounds. it is now clear that some compounds are activated by other oxidizing… More

Glutaryl-coa dehydrogenase (gcdh), an enzyme common to lysine, hydroxylysine, and tryptophan catabolism, catalyzes the conversion of glutaryl-coa to crotonyl-coa. lack of gcdh activity in humans is characterized by excretion of massive amounts of glutaric acid and 3-hydroxyglutaric acid, thus… More

Prostacyclin synthase (pgi2 synthase) catalyzes an intramolecular redox reaction in which prostaglandin endoperoxide, pgh2, is converted to prostacyclin, pgi2. the potent biological activities of pgi2 indicate an important role for prostacyclin synthase in the pathophysiology of thrombosis and… More

Lipoxgenases constitute a famly of non-heme iron-containing dioxygenases that have been demonstrated to produce a wide range physiologically active metaboites. the enzyme 12-lipoxygenase (12-lx) is present in platelets, leukosytes, lung and brain. 12-lx converts arachidonic acid to 12-hpete, which… More

Prostaglandin E isomerase (known as PGE2 synthase also) catalyses the isomerization reaction in which prostaglandin endoperoxide (PGH2) is converted to PGE2. The potent biological activities of PGE2 indicate an important role for prostaglandin E isomerase in the pathogenesis of periodontal disease,… More

Linoleic acid, the predominant polyunsaturated fatty acid (PUFA) in the human diet, can bemetabolized by cyclooxgenase, lipoxygenase and P450 enzymes. The monohydroxy derivatives oflinoleic acid, 9(S)-HODE and 13 (S)-HODE, are the most widely distributed of the known linoleic acidmetabolites. These… More

The development of cancer is a complex process that appears to involve multiple mechanisms.Recent studies indicate that the Her-2/neu (ERBB2) gene may be important in the transformation ofnormal breast epithelial cells to a cancerous phenotype. In reality, more than one-half of breast cancersare… More

A novel class of postaglandin F2-like compounds formed in vitro or in vivo by a free-radical catalyzed noncyclocxygenase mechanism have recently been discovered. For normal humans. Levels of these compounds (called F2-isoprostanes) range from 5-50 pg/ml plasma and 500-3000 pg/ml urinary creatinine,… More

We will develop and market a comprehensive collection of antibodies specific for enzymes that play a significant role in drug metabolism . Availability of specific antibodies will greatly facilitate studies of polymorphisms, species and tissue distribution of drug metabolizing enzymes, and the role… More

Linoleic acid, the predominant polyunsaturated fatty acid (PUFA) in the human diet, is a substratecyclooxygenase, lipoxygenase and cytochrome P450 enzymes. The majore metabolitcs of these pathways,13(S)-HODE, 9, 10-epoxyoctadecenoate, and 12, 13-epoxyoctadecenoate are known to exhibit… More

The vast majority of studies on prostanoid metabolism have focused on prostaglandin E2, prostacyclithromboxane A2, and the leukotrienes, which are collectively involved in the regulation of a wide rapathophysiological events. Although it has been the subject of less intense investigation, it has… More

This project will develop methods for large scale production and quantification of humanprostaglandin H synthase-2 (PGHS-2), a recently discovered enzyme that is differentially regulated andhas significantly different properties than the pGHS-1. Data obtained to date in experimental systemssuggest… More

DESCRIPTION (Applicant's abstract): Accumulating evidence suggests oxidative stress is responsible for altered metabolic functions in various pathophysiological conditions including cancer, cardiovascular disease and aging. The production of reactive oxygen… More

DESCRIPTION (provided by applicant): This project will explore the application of a dual-secondary column comprehensive two-dimensional gas… More

Colorectal cancer is a leading cause of death in the United States. There is very strong evidence that screening for this disease can reduce colorectal cancer mortality. Present screening methods include fecal occult blood testing (FOBT) and endoscopy, which can detect some early colon cancers and… More

DESCRIPTION (provided by applicant): Accumulating evidence suggests that sustained oxidative stress affects many biochemical and molecular processes and is responsible for altered metabolic functions in various pathophysiological conditions including cancer, cardiovascular disease and aging. … More

DESCRIPTION (provided by applicant): Accumulating evidence suggests that sustained oxidative stress affects many biochemical and molecular processes and is responsible for altered metabolic functions in various pathophysiological conditions including cancer, cardiovascular disease and aging. … More

DESCRIPTION (provided by applicant): Biomarkers that accurately reflect acute and/or past exposure to harmful agents are crucial in any study aiming to reduce the incidence of diseases resulting from environmental chemicals or other exposures. The biomarkers evaluated to date in biological fluids… More

DESCRIPTION (provided by applicant): Biomarkers that accurately reflect acute and/or past exposure to harmful agents are crucial in any study aiming to reduce the incidence of diseases resulting from environmental chemicals or other exposures. The biomarkers evaluated to date in biological fluids… More

DESCRIPTION (provided by applicant): Environmental agents with estrogen-like activity are a major public health issue. Although a variety of assays have been developed to detect binding to the estrogen receptor (ER) and other assays have been developed to monitor subsequent effects on estrogen… More

DESCRIPTION (provided by applicant): Current biomarkers employed in the detection of organ toxicity are often not sensitive enough to detect the early stages of acute organ damage, i.e. at a stage when reducing or eliminating exposure to a toxin could prevent progression of organ damage or a disease… More