Public health implications of hazardous waste sites: Findings, assessment and research

Rosa, Christopher T. De; Johnson, B.; Fay, Mike; Hansen, Henrik; Mumtaz, M.M.

doi:10.1016/s0278-6915(97)00084-7

Cited by 52 publications

(16 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Later in life, children can be exposed to PCBs in the same manner as adults. Because of their smaller weight, a child's intake of PCB/kg body weight (for a given amount of contaminated product consumed) would be greater than in an adult (De Rosa et al, 1997;Barbalace, 2003).…”

Section: Introductionmentioning

confidence: 99%

Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls

Horváthová¹,

Jahnová²,

Palkovičová³

et al. 2011

Journal of Immunotoxicology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls

Horváthová¹,

Jahnová²,

Palkovičová³

et al. 2011

Journal of Immunotoxicology

View full text Add to dashboard Cite

“…The United States produces in excess of 130,000 tons of TCE per year (11), making it the most widespread chemical contaminant in both soil and ground water. TCE is readily absorbed into the body where it can enter the glutathione conjugation detoxification pathway producing the mercapturic acid N-acetyl-S-1,2-dichlorovinyl-L-cysteine (NA-DCVC) for subsequent urinary excretion (12,13).…”

mentioning

confidence: 99%

Structures of aminoacylase 3 in complex with acetylated substrates

Hsieh

Tsirulnikov²,

Sawaya³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Trichloroethylene (TCE) is one of the most widespread environmental contaminants, which is metabolized to N-acetyl-S-1,2-dichlorovinyl-L-cysteine (NA-DCVC) before being excreted in the urine. Alternatively, NA-DCVC can be deacetylated by aminoacylase 3 (AA3), an enzyme that is highly expressed in the kidney, liver, and brain. NA-DCVC deacetylation initiates the transformation into toxic products that ultimately causes acute renal failure. AA3 inhibition is therefore a target of interest to prevent TCE induced nephrotoxicity. Here we report the crystal structure of recombinant mouse AA3 (mAA3) in the presence of its acetate byproduct and two substrates: N α -acetyl-L-tyrosine and NA-DCVC. These structures, in conjunction with biochemical data, indicated that AA3 mediates substrate specificity through van der Waals interactions providing a dynamic interaction interface, which facilitates a diverse range of substrates.mercapturates | metalloprotein | X-ray structure A minoacylase 3 (AA3) is a member of the aminoacylase family of enzymes that deacylates a broad range of substrates including both N α -acetylated amino acids and S-cysteine conjugates of N-acetyl-L-cysteine (mercapturic acids) ( Fig. 1) (1). There are three types of aminoacylases: (i) aminoacylase 1 (AA1) deacetylates neutral aliphatic N-acyl-α-amino acids and mercapturic acids; (ii) aminoacylase 2 or aspartoacylase (AA2) has a strict specificity for N α -acetyl-L-aspartate (NAD); and (iii) aminoacylase 3 (AA3) preferentially deacetylates N α -acetylated aromatic amino acids and mercapturic acids that are usually not deacetylated by AA1 (1-6). Despite different substrate specificities, AA2 and AA3 have a high degree of sequence (42% identity) and structure homology but are both substantially different from AA1 (∼10% of sequence identity) (2, 6-10).AA3 is of particular interest for human health because it participates in mediating toxicity of the xenobiotic trichloroethylene (TCE). The United States produces in excess of 130,000 tons of TCE per year (11), making it the most widespread chemical contaminant in both soil and ground water. TCE is readily absorbed into the body where it can enter the glutathione conjugation detoxification pathway producing the mercapturic acid N-acetyl-S-1,2-dichlorovinyl-L-cysteine (NA-DCVC) for subsequent urinary excretion (12, 13). However, NA-DCVC can be deacetylated by AA3-which is highly expressed in the renal proximal tubule, liver, and brain-to generate S-1,2-dichlorovinyl-L-cysteine (DCVC) (2) and further transformed via β-lyases or flavin monooxygenases into lethal products capable of causing acute renal failure and toxicity to the liver and brain. (4, 13-22). Thus, inhibition of AA3 can decrease DCVC formation and ameliorate TCE toxicity, presenting a potential target for drug discovery.Generating specific inhibitors for AA3 would be greatly aided by high-resolution structural data, but structural studies of aminoacylases have been limited to AA1 (7) and AA2 (8, 9), which differ in both overall architecture and ac...

show abstract

“…In fact, because of high As (and other metal) concentrations in the drinking water supplies in many countries, chronic toxicity and development of neoplastic lesions have become health problems of global proportions (1,2). In the United States, As, Cd, Cr, and Pb are the top four metals in site frequency count by the Agency for Toxic Substances and Disease Registry (ATSDR) Completed Exposure Pathway Site Count Report (3); three of these, As, Pb, and Cd, are among the Superfund's top 10 priority hazardous substances (4). In addition, these metals most often occur together; they are present in 8 of 10 and 5 of 10 of the top 10 binary combinations of contaminants in soil and water, respectively (5).…”

mentioning

confidence: 99%

Characterization of gene expression changes associated with MNNG, arsenic, or metal mixture treatment in human keratinocytes: application of cDNA microarray technology.

Bae

Hanneman

Yang

et al. 2002

Environ Health Perspect

View full text Add to dashboard Cite

Public health implications of hazardous waste sites: Findings, assessment and research

Cited by 52 publications

References 7 publications

Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls

Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls

Structures of aminoacylase 3 in complex with acetylated substrates

Characterization of gene expression changes associated with MNNG, arsenic, or metal mixture treatment in human keratinocytes: application of cDNA microarray technology.

Contact Info

Product

Resources

About