Title: Toxicological Sciences

Title: Toxicological Sciences

ISO Abbreviated Title: Toxicol. Sci.

JCR Abbreviated Title: Toxicol Sci

ISSN: 1096-6080

Issues/Year: 12

Journal Country/Territory: United States

Language: English

Publisher: Oxford Univ Press

Publisher Address: Great Clarendon St, Oxford OX2 6DP, England

Subject Categories:

Toxicology: Impact Factor 3.088, 10/75 (2005)

? Garcia Arenas, G., Claudio, L., Perez Severiano, F. and Rios, C. (1999), Lead acetate exposure inhibits nitric oxide synthase activity in capillary and synaptosomal fractions of mouse brain. Toxicological Sciences, 50 (2), 244-248.

Full Text: 1999\Tox Sci50, 244.pdf

Abstract: The toxicity of lead (Pb) is of concern to public health due to its persistence in the environment. Brain is one of the major target organs where severe neurologic alterations may be triggered after exposure. The primary effects of lead on brain functions are thought to be a damage to the nervous system microvasculature. However, the mechanism of this toxicity is poorly understood. Nitric oxide synthase (NOS) may be a target for lead and changes in its function can result in a cascade of pathophysiological effects that may be observed in isolated capillaries and synaptosomes. We have determined the concentration of lead in blood, capillaries and synaptosomes in brain from mice receiving 0, 250, 500, and 1000 ppm of lead for 14 days, through the drinking water. NOS activity was determined in the capillaries and synaptosomes by following the conversion of H-3-L-arginine to H-3-L-citrulline. The results show that blood lead levels were dose-dependent. Brain capillaries showed a preferential accumulation of lead as compared to synaptosomes. With all Pb treatments, synaptosomal constitutive NOS was inhibited (about 50% of control) while the inducible NOS activity in capillaries was enhanced. These data suggest that inhibition of cNOS activity and increase in iNOS may contribute to the Pb effects on the CNS.

? Phillips, T.D. (1999), Dietary clay in the chemoprevention of aflatoxin-induced disease. Toxicological Sciences, 52 (2 SS), 118-126.

Full Text: Tox Sci52, 118.pdf

Abstract: Aflatoxins are harmful by-products of mold growth and, though invisible to the naked eye, are potentially fatal. The aflatoxin problem is long-standing and inextricable. Concerns about the aflatoxins originate from the strong implications of their involvement in disease and death in humans and animals, yet scientists and clinicians are still seeking ways to effectively deal with these dangerous and elusive chemicals. Safe, practical, and effective strategies for the detoxification of aflatoxin-contaminated food and feed are highly desirable. A simple and effective approach to the chemoprevention of aflatoxicosis has been to diminish or block exposure to aflatoxins via the inclusion of HSCAS clay in the diet. HSCAS clay acts as an a aflatoxin enterosorbent that tightly and selectively binds these poisons in the gastrointestinal tract of animals, decreasing their bioavailability and associated toxicities, Further studies to delineate the molecular mechanisms of action have shown that the dicarbonyl system of aflatoxin is essential for tight binding by HSCAS. In these studies, adsorption data was fitted to multiple isotherm equations including the Langmuir, multi-Langmuir, general Freundlich, Langmuir-Freundlich, Tóth and various transforms. Information derived included: the Gibbs standard free energy change of adsorption, enthalpy of adsorption, capacity, affinity, and heterogeneity coefficient. Computer modeling was also utilized to provide additional structural information and insight into the mechanism. Evidence suggests that aflatoxins may react at multiple sites on HSCAS particles, especially the interlayer region, but also at edges and basal surfaces. Since clay and zeolitic minerals comprise a broad family of functionally diverse chemicals, there may be significant hidden risks associated with their indiscriminate inclusion in the diet, All aflatoxin binding agents should be rigorously tested, paying particular attention to their effectiveness and safety in aflatoxin-sensitive animals and their potential for interactions with critical nutrients.

Keywords: Sodium-Calcium Aluminosilicate, Growing-Pigs, In-Vitro, Toxicity, Efficacy, Prevention, Sorbent, Zearalenone, Adsorption, Reduce, Clay, Hscas Clay, Chemoprevention, Chemoprotection, Chemoprophylaxis, Enterosorbent, Aflatoxin, Aflatoxicosis, Primary Hepatic Cancer, Sorption, Aflatoxin Binder, Detoxification

? Bae, D.S., Gennings, C., Carter, W.H., Yang, R.S.H. and Campain, J.A. (2001), Toxicological interactions among arsenic, cadmium, chromium, and lead in human keratinocytes. Toxicological Sciences, 63 (1), 132-142.

Full Text: 2001\Tox Sci63, 132.pdf

Abstract: To evaluate health effects of chemical mixtures, such as multiple heavy metals in drinking water, we have been developing efficient and accurate hazard identification strategies. Thus, in this study, we determine the cytotoxicity of arsenic, cadmium, chromium, and lead, and characterize interactions among these metals in human epidermal keratinocytes. Three immortal keratinocyte cell lines (RHEK-1, HaCaT, and NM1) and primary keratinocytes (NHEK) were. used. A statistical approach applying an additivity response surface methodology was used to test the validity of the additivity concept for a 4-metal mixture. Responses of the 4 keratinocyte strains to the metal mixture were highly dose-dependent. A growth stimulatory effect (hormesis) was observed in RHEK-1, NM1, and NHEK cells with the metal mixture at low concentrations (low ppb range). This hormesis effect was not significant in HaCaT. As the mixture concentration increased, a trend of additivity changed to synergistic cytotoxicity in all 4 cell strains. However, in NHEK, RHEK-1, and HaCaT, at the highest mixture concentrations tested, the responses to the metal mixtures were antagonistic. In NM1, no significant antagonistic interaction among the metals was observed. To explore a mechanistic basis for these differential sensitivities, levels of glutathione and metallothioneins I and II were determined in the keratinocyte cell strains. Initial data are consistent with the suggestion that synergistic cytotoxicity turned to antagonistic effects because at highest mixture exposure concentrations cellular defense mechanisms were enhanced.

Keywords: Keratinocytes, Toxicological Interactions, Additivity Response Surface, GSH, MT, Human Epidermal-Keratinocytes, Hamster Ovary Cells, Heat-Shock Protein, I/II Null Mice, Chemical Hormesis, Neoplastic Transformation, Sodium Arsenite, Gene-Expression, Growth-Factors, Metallothionein