Projects

Darryl B.Hood, Ph.D. and Michael Aschner, Ph.D.

The central hypothesis to be tested is that gestational exposure to B(a)P aerosol in C57BL mice at levels observed in humans in certain environments results in lifelong learning and memory deficits. Further, if these deficits are mediated in part through modulation of developmental NMDA/AMPA glutamate receptor subunit expression at a time when excitatory synapses are being formed in the hippocampus and somatic sensory cortex.

Effect of B(a)P Exposure on Dopaminergic Mechanisms (Pilot)

Twum-Ampofo Ansah, Ph.D., and Ariel Y. Deutch, Ph.D.

Studies have shown that acute exposure to B(a)P and fluoroanthene produces a variety of behavioral deficits that are specific to the nervous system, including decreased motor activity and responsiveness to sensory stimuli. The neurochemical pathways mediating these effects have not been elucidated but there are indications that the dopaminergic pathway may be involved.  Evidence also shows that B(a)P crosses the blood-brain barrier. This study will ask if sub acute inhalation exposure to B(a)P in C57BL/6J mice will decrease loco motor activity, if reactive metabolites of B(a)P and markers of oxidative stress are localized to dopaminergic regions of the brain implicated in motor function and if there is altered susceptibility to B(a)P in mice also over expressing antioxidant enzymes

B(a)P Induced Activation of Prostatic Specific Genes (Pilot)

Ben Ogunkua, Ph.D., and Robert J. Matusik, Ph.D.

The incidence of advanced prostate cancer and mortality is disproportionately high in some populations exposed to environmental polycyclic aromatic hydrocarbons like B(a)P. To determine if B(a)P alters the rate or extent of cancer development, the collaborators will study a genetically engineered LPB-Tag transgenic mouse that develops a pathological pattern of preneoplastic lesions along with small foci of locally invasive carcinoma, ultimately leading to prostate cancer. The study will ask if B(a)P alters steroid and androgen-dependent events in a temporal manner, thus altering prostate function, and/or if B(a)P accelerates progression from small lesions to full prostate adenocarcinoma..

Dietary Fat Potentiation of B(a)P Induced Colon Cancer (Pilot)

Aramandla Ramesh, Ph.D., and Jason D. Morrow, M.D.

Every year 56,000 deaths are attributable to colorectal cancer in the US, and consumption of well-done red meat and saturated fats, rich in PAH's, may be a causative factor. This study asks if the formation and progression of colon tumors in adult ApcMin mice is influenced by the oral ingestion of saturated fat containing B(a)P.This will include an analysis of the role of dietary fat in any B(a)P-induced oxidative damage and isoprostane production and B(a)P-DNA adduct formation.