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B W Wilson

Publications and source records attributed to B W Wilson.

At least 91 records · Page 5Linked to original sources

Percutaneous absorption and dermal dose-cholinesterase response studies with parathion and carbaryl in the rat.

Dermal dose-ChE response (toxicity) and percutaneous absorption of parathion and carbaryl were studied in the rat. Parathion was as toxic to young animals as it was to adults of the same sex and more toxic to adult females than to adult males. Carbaryl was nontoxic at administered dosages. In each percutaneous absorption study, [14C]parathion or [14C]carbaryl was applied to back skin (12.5-13.8 cm2) at 43.5 to 48 micrograms/cm2. Thirty-six rats were treated and three were killed at time intervals between 0.5 and 168 hr. The area of the skin which had been treated, plasma, heart, liver, kidneys, urine, feces, and the remaining carcass were analyzed for 14C. Recovery studies indicated that adult male and female rats, respectively, absorbed 59.2 and 57.0% of the applied parathion, while adult males absorbed 57.7% of the applied carbaryl. Parathion was lost from skin (t1/2, 28.6 hr) more rapidly than carbaryl (t1/2, 40.6 hr). Approximately 1.4 and 5.8%, respectively, of the applied parathion and carbaryl penetrated the skin within 1 hr and was available for absorption. Parathion was absorbed through skin of adult male and female rats, respectively, at rates of 0.33 and 0.49 micrograms hr-1 cm-2. Carbaryl was absorbed by male rats at the rate of 0.18 micrograms hr-1 cm-2. The half-lives for absorption of parathion by blood ranged between 0.38 and 2.1 hr, while elimination half-lives ranged between 28.6 and 39.5 hr. Carbaryl absorption and elimination half-lives were 1.26 and 67 hr, respectively.

Animals↗

Fractionation of skin tumor-initiating activity in coal liquids.

Narrow temperature range distillates from biologically active solvent refined coal-I and -II heavy-end coal liquids were fractionated according to chemical class and assayed for initiation of skin carcinogenesis in CD-1 mice. In addition, instrumental chemical analyses were performed on the distillates and their chemical fractions. Results showed that initiation activity in these complex fuel mixtures could be segregated both by boiling point and chemical class. Neutral polycyclic aromatic hydrocarbon fractions were the most active of the chemical classes, with some initiating activity being shown by nitrogen-containing polycyclic aromatic hydrocarbon. Aliphatic and hydroxylated polycyclic aromatic hydrocarbon fractions showed little or no initiating activity. For the two solvent refined coal-II distillates studied, initiating activity was substantially higher in the material boiling above 850 degrees F than in that boiling 800-850 degrees F, although both contained essentially the same concentrations of benzo[a]pyrene. These data indicate that the overall initiating activity of these complex mixtures is highly dependent on interactions of the many chemical carcinogens and that relative concentrations of known carcinogenic polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and dimethylbenz[a]anthracene, are not the sole determinants of initiating activity.

Animals↗

Percutaneous toxicity and delayed neurotoxicity of organophosphates in the scaleless hen.

The acute toxicity of tri-ortho-cresyl phosphate (TOCP) and the development of delayed neurotoxicity were characterized in the scaleless hen, a featherless mutant, and compared to the responses observed in normally feathered birds. Brain acetylcholinesterase (AChE) activity was comparable between scaleless and normal hens, but nonspecific cholinesterase (ChE) activities of brain and plasma were significantly higher in scaleless birds. The acute ID50 of TOCP for plasma ChE activity was 690 mg/kg for scaleless birds and 240 mg/kg for normal ones following sc administration. However, there was no difference in the ID50 for plasma ChE activity between normal and scaleless hens treated sc with the active metabolite of TOCP, 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphoran-2-one, or parathion. The onset of clinical signs of delayed neurotoxicity in scaleless birds was 8 to 14 days after sc or dermal treatment with TOCP and caused typical axonal fragmentation in the sciatic nerve. Plasma creatine phosphokinase activity was significantly increased following the onset of delayed neurotoxicity in both lines of birds. Dermal application of TOCP to a 50-cm2 area on the backs of scaleless hens inhibited plasma ChE activity in a dose-related manner (ID50 = 115 mg/kg), and the lowest dose of TOCP, 114 mg/kg, did not produce delayed neurotoxicity. The results show that the scaleless hen can be used to determine a no-observable effect level for delayed neurotoxicity which regulatory agencies could use to extrapolate a safe level of human dermal exposure to organophosphates that produce delayed neurotoxicity.

Acetylcholinesterase↗

Recovery of acetylcholinesterase forms in quail muscle cultures after intoxication with diisopropylfluorophosphate.

Studies of recovery of acetylcholinesterase (AChE, EC 3.1.1.7) after inhibition by organophosphates (OPs) have been hampered by the low number of in vitro systems with large collagen-tailed forms of AChE characteristic of motor end plates. Pectoral muscle cultures from Japanese quail with high levels of a large 20S form of AChE were used to study recovery of cells from acute treatment with diisopropylfluorophosphate (DFP), an irreversible AChE inhibitor. Low molecular weight AChE forms were synthesized more rapidly than the large 20S form following a 15-min treatment with 10(-4)M DFP. Most of the activities of the small forms, but only part of the activity of the 20S form, disappeared within 48 hr after cycloheximide was added to block protein synthesis. To the contrary, virtually all the activity of the 20S AChE that was newly synthesized after DFP treatment was lost within 24 hr after cycloheximide treatment. The results were generally consistent with the idea that the 20S AChE form is assembled inside the cell near to its surface and then is released to bind to its outside.

Acetylcholinesterase↗

Water deprivation: beneficial effect on muscular dystrophy in chickens.

Chicks affected with hereditary muscular dystrophy were deprived of water for 1 to 4 days at ages to 37 days ex ovo. Water deprivation partially alleviated impaired righting ability and reduced the typically elevated plasma creatine kinase activity by as much as 90%. Muscles from water-deprived chicks showed several qualitative histologic improvements, including decreased sarcoplasmic staining for acetylcholinesterase activity, reduced fiber diameters, and a decreased incidence of abnormally large rounded fibers, but retained the high degree of fiber diameter variability characteristic of dystrophic muscles. Feed deprivation reduced body weight to a similar extent as water deprivation but had lesser effects on creatine kinase activity and did not improve righting ability or muscle histology. Although the mechanism of the improvements is unknown, the magnitude and scope of the effects suggest that water deprivation beneficially alters a major abnormality in dystrophic chickens.

Animals↗

Regulation of acetylcholinesterase forms in quail and chicken muscle cultures.

High molecular forms of acetylcholinesterase (AChE) have been difficult to obtain in primary cultures of muscle from mammals and birds. This research used pectoral muscle cultures from Japanese quail and chick embryos grown in medium containing embryo extract and horse serum to study the growth and extraction conditions necessary for study of high molecular weight 20S AChE forms found in these birds. The results confirmed the presence of a 20S AChE form in quail muscle cultures and showed that its extraction from the cells was considerably improved by using a Mg-cholate extraction buffer rather than the more commonly used NaCl-Triton X buffer. A striking finding was that removal of serum from the medium for 1-2 days caused the preferential increase in a 20S form in the quail and the resolution of one from background activity in chick muscle cultures. Removal of embryo extract had no effect on levels of the AChE forms. The results suggest that serum factors inhibit the formation of the high molecular weight, motor end plate associated form of AChE in aneural cultures of avian muscle, and that effects of factors such as neural extracts and nerves on AChE forms in cultured muscle should be examined using a defined basal media.

Acetylcholinesterase↗

Chronic exposure to 60-Hz electric fields: effects on pineal function in the rat.

As a component of studies to search for effects of 60-Hz electric field exposure on mammalian endocrine function, concentrations of melatonin, 5-methoxytryptophol, and serotonin-N-acetyl transferase activity were measured in the pineal glands of rats exposed or sham-exposed at 65 kV/m for 30 days. In two replicate experiments there were statistically significant differences between exposed and control rats in that the normal nocturnal increase in pineal melatonin content was depressed in the exposed animals. Concentrations of 5-methoxytryptophol were increased in the pineal glands of the exposed groups when compared to sham-exposed controls. An alteration was also observed in serotonin-N-acetyl transferase activity, with lower levels measured in pineal glands from exposed animals.

Animals↗

Relative concentrations of polyaromatic primary amines and azaarenes in mutagenically active nitrogen fractions from a coal liquid.

Thin-layer chromatography (TLC) was used to separate components in the basic and tar fractions of solvent refined coal (SRC-I) process solvent (PS) to obtain materials suitable for biological and chemical analysis. Those fractions eluted from TLC plates which were mutagenically active in the Ames/Salmonella assay were analyzed by gas chromatographic mass spectrometry (GCMS) for polycyclic azaarenes, polyaromatic primary amines (PAA) and carbazoles. In all materials tested, a strong correlation was observed between the concentration of PAAs in a given TLC region and the mutagenicity of that region in the Ames assay system. Conversely, azaarenes having 2--4 fused rings and carbazoles were present in both mutagenic and non-mutagenic TLC eluates. No PAAs were detected in mutagenically inactive TLC eluates. In comparison to the mutagenic tar fractions, the PS basic fraction contained relatively larger concentrations of 2- and 3-ringed components such as aminonaphthalenes and aminoanthracenes or aminophenanthrenes. The tar fractions, which were essentially devoid of aminonaphthalenes, had a higher average molecular weight and contained relatively higher concentrations of aminopyrenes.

Amines↗

Paraoxon increases the rate of synthesis of acetylcholinesterase in cultured muscle.

Acetylcholinesterase (AChE) activity of cultured chick embryonic pectoral muscle was significantly increased above control activity during recovery from brief treatments with paraoxon (O, O-diethyl-p-nitrophenyl phosphate), the anticholinesterase metabolite of parathion. Paraoxon also increased the rate of degradation of the enzyme, suggesting the higher AChE activity of paraoxon-treated cells was due to a stimulation of enzyme synthesis.

Acetylcholinesterase↗

Alteration of acetylcholine receptor and acetylcholinesterase metabolism by actinomycin D in cultured muscle cells.

Actinomycin D (ACT-D), an inhibitor of transcription, was added to chick muscle cultures to study its effect on the synthesis of acetylcholine receptor (ACHR) and acetylcholinesterase (ACHE, EC 3.1.1.7). Doses of ACT-D (1.85-18.5 nM), which inhibited uridine incorporation up to 80%, increased ACHR, ACHE, and creatine kinase (CK, EC 2.7.3.2) levels without affecting general cell protein. Degradation of ACHR was slower in ACT-D treated cultures than controls, resulting in a twofold increase in receptor half-life. Uridine incorporation was inhibited by ACT-D in both mononucleated cells and myotubes and [3H]uridine nuclear grain distribution were shifted to values lower than controls. The results indicate that posttranscriptional effects of ACT-D increase levels of ACHR, ACHE, and CK and that decreased degradation could account for the increase in the number of surface ACH receptors.

Acetylcholinesterase↗

Molecular forms of acetylcholinesterase in chick embryonic fast muscle: developmental changes and effects of DFP treatment.

Multiple molecular forms of acetylcholinesterase (AChE) from embryonic chick pectoral muscle were examined by sucrose density sedimentation. Embryonic muscle in ovo possessed three molecular forms with apparent sedimentation coefficient of 7S, 11S, and 20S. The proportion of the 20S form increased 4-fold between days 11 and 18 in ovo and there was a decrease in the proportion of the 7S and 11S forms. Cultured embryonic muscle contained only 7S and 11S AChE despite the presence of the 20S form in the tissue from which the cultures were derived. Brief treatment with diisopropylphosphorofluoridate (DFP) completely inhibited the enzyme activity; the newly synthesized AChE first appeared as a 7S form. Polyacrylamide gel electrophoresis of the peak fractions from the sucrose gradients revealed that the 7S AChE was composed of two electrophoretic forms and gave evidence that the 20S AChE was too large to enter the running gel. The results are consistent with the ideas that the distribution of AChE molecular forms is regulated during embryonic development and that AChE is first synthesized as a low molecular weight form following inhibition with organophosphate compounds.

Acetylcholinesterase↗