■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

Impacts of pollution on coastal and marine ecosystems including coastal and marine fisheries and approach for management: a review and synthesis.

Arsenic-induced oxidative stress and its reversibility

Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children's exposure to pesticides and other environmental agents, and thereby reduce the incidence of environmentally related disease.

Exposures of children to organophosphate pesticides and their potential adverse health effects.

Synthetic chemicals are released into the environment by design (pesticides) or as a result of industrial activity. It is well known that natural environmental chemicals can cause goiter or thyroid imbalance. However, the effects of synthetic chemicals on thyroid function have received little attention, and there is much controversy over their potential clinical impact, because few studies have been conducted in humans. This article reviews the literature on possible thyroid disruption in wildlife, humans, and experimental animals and focuses on the most studied chemicals: the pesticides DDT, amitrole, and the thiocarbamate family, including ethylenethiourea, and the industrial chemicals polyhalogenated hydrocarbons, phenol derivatives, and phthalates. Wildlife observations in polluted areas clearly demonstrate a significant incidence of goiter and/or thyroid imbalance in several species. Experimental evidence in rodents, fish, and primates confirms the potentiality for thyroid disruption of several chemicals and illustrates the mechanisms involved. In adult humans, however, exposure to background levels of chemicals does not seem to have a significant negative effect on thyroid function, while exposure at higher levels, occupational or accidental, may produce mild thyroid changes. The impact of transgenerational, background exposure in utero on fetal neurodevelopment and later childhood cognitive function is now under scrutiny. There are several studies linking a lack of optimal neurological function in infants and children with high background levels of exposure to polychlorinated biphenyls (PCBs), dioxins, and/or co-contaminants, but it is unclear if the effects are caused by thyroid disruption in utero or direct neurotoxicity.

Effects of Environmental Synthetic Chemicals on Thyroid Function

Arsenic-induced histopathology and synthesis of stress proteins in liver and kidney of Channa punctatus.

Selective low (15 mg sodium fluoride (NaF)/L) and relatively high (150 mg NaF/L) doses of in vivo fluoride (F) treatment to Swiss albino mice through drinking water elicited organ-specific toxicological response. All the F-exposed groups showed severe alterations in both liver and kidney architectures, but there was no significant change in the rate of water consumption and body weight. Vacuolar degeneration, micronecrotic foci in the hepatocytes, and hepatocellular hypertrophy were evident in the mice exposed to low dose (15 mg NaF/L for 30 days) while sinusoidal dilation with enlarged central vein surrounded by deep-blue erythrocytes were preponderant when treated with the same dose for a period of 90 days. Blood filled spaces, disintegration of tubular epithelium, and atrophy of glomeruli were also recorded in the kidney of the same treatment group. Change in reduced glutathione level (GSH), glutathione-s-transferase (GST) activity, malondialdehyde (MDA) production in both liver and kidney, disturbances in liver function, induction of heat shock protein 70 (Hsp 70) expression in kidney and its down regulation in liver were positively correlated with histopathological lesion.

Shelley Bhattacharya

Papers

Arsenic-induced histopathology and synthesis of stress proteins in liver and kidney of Channa punctatus.

Fluoride-induced histopathology and synthesis of stress protein in liver and kidney of mice

Low dose of arsenic trioxide triggers oxidative stress in zebrafish brain: expression of antioxidant genes.

Induction of oxidative stress by arsenic in Clarias batrachus: involvement of peroxisomes.

Antioxidant responses of the earthworm Lampito mauritii exposed to Pb and Zn contaminated soil