Michael J. McCabe

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Mercury is widespread in the environment and consequently there are large populations that are currently exposed to low levels of mercury as a result of ubiquitous environmental factors. Whether these environmental levels of mercury are harmful is a matter of current debate, with epidemiological and animal studies suggesting detrimental effects on the(More)
Chronic ingestion of arsenite-contaminated drinking water causes skin, bladder, and liver cancer. The mechanism of arsenite-induced carcinogenesis is unknown. Arsenite is known to disrupt mitosis and to delay transit through M phase in normal diploid fibroblasts. SV40-transformed human fibroblasts were observed to be hypersensitive to the cytotoxic and(More)
Arsenic trioxide, an acute promyelocytic leukemia chemotherapeutic, may be an efficacious treatment for other cancers. Understanding the mechanism as well as genetic and molecular characteristics associated with sensitivity to arsenite-induced cell death is key to providing effective chemotherapeutic usage of arsenite. Arsenite sensitivity correlates with(More)
The immunotoxic environmental pollutant tri-n-butyltin (TBT) kills thymocytes by apoptosis through a mechanism that requires an increase in intracellular Ca2+ concentration. The addition of TBT (EC50 = 2 microM) to fura-2-loaded rat thymocytes resulted in a rapid and sustained increase in the cytosolic free Ca2+ concentration ([Ca2+]i) to greater than 1(More)
The effect of oral administration of lead, as Pb-acetate, via the drinking water on the murine delayed type hypersensitivity (DTH) response was investigated. The DTH response of BALB/c mice sensitized intravenously with sheep red blood cells (SRBC) was found to be suppressed markedly in lead-intoxicated mice. Suppression of the DTH correlated with(More)
BACKGROUND Thymocyte apoptosis has been shown to be regulated by intracellular levels of cations. Elevation of [Ca2+]i can induce cell death by apoptosis, whereas, Zn2+ prevents it. EXPERIMENTAL DESIGN A membrane permeable metal ion chelator, N,N,N'N',-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN), was used to examine the role of intracellular zinc in(More)
The ubiquitous environmental heavy metal contaminant mercury (Hg) is a potent immunomodulator that has been implicated as a factor contributing to autoimmune disease. However, the mechanism(s) whereby Hg initiates or perpetuates autoimmune responses, especially at the biochemical/molecular level, remain poorly understood. Recent work has established a(More)
Arsenic induces clinical remission in patients with acute promyelocytic leukemia and has potential for treatment of other cancers. The current study examines factors influencing sensitivity to arsenic using human malignant melanoma cell lines. A375 and SK-Mel-2 cells were sensitive to clinically achievable concentrations of arsenite, whereas SK-Mel-3 and(More)
Occupational or environmental exposure to metals is believed to affect human health adversely. One mechanism whereby metals can alter health is through modulation of immune homeostasis. Imbalances in immune regulation by metals can lead to inadequate or excessive production of inflammatory cytokines. Alternatively, metals can lead to inappropriate(More)