PubMed Health⌕ Search

Biomedical subjects

F W Sunderman

Publications and source records attributed to F W Sunderman.

At least 109 records · Page 6Linked to original sources
PubMed1979

Eye malformations in rats: induction by prenatal exposure to nickel carbonyl.

Exposure of pregnant rats to inhalation of nickel carbonyl on days 7 or 8 of gestation frequently causes the progeny to develop ocular anomalies, including anophthalmia and microphthalmia. The incidence of extraocular anomalies is very low. The specificity of nickel carbonyl for induction of ocular anomalies in rats appears to be unique among known teratogenic agents.

Abnormalities, Drug-Induced↗
PubMed1979

Increased serum erythropoietin activity in rats following intrarenal injection of nickel subsulfide.

To investigate the pathophysiologic mechanisms of nicekl-induced erythrocytosis, serum erythropoietin activities were measured in (a) pooled serum from rats at 2 wk after intrarenal injection of alpha Ni3S2 (5 mg/rat), and (b) pooled serum from control rats at 2 wk after intrarenal injection of sterile NaCl vehicle (0.4 ml/rat). A sensitive erythropoietin bioassay was employed, which entailed repetitive administration of test serums to post-hypoxic polycythemic mice in divided doses (12 s.c. injections of 0.5 ml of serum at 6 hr intervals for 3 da; total dose = 6 ml of serum/mouse). The erythropoietin detection limit was congruent to 20 I.U./liter of serum. In mice which received pooled serum from alpha Ni3S2-treated rats, erythrocyte 59Fe-uptake averaged 28% (S.D. +/- 5) (vs 3.7 +/- 1.1% in control rats; P less than 0.001). Based upon a 7-point calibration plot, the erythropoietin activity in pooled serum from alpha Ni3S2-treated rats averaged 130 I.U./liter (S.D. +/- 18) (vs 27 +/- 6 I.U./liter in control rats; P less than 0.001). In vitro addition of Ni(II) to rat serum (100 microgram/liter) had no effect upon serum erythropoietin activity. This study demonstrates that induction of erythrocytosis in rats by intrarenal injection of alpha Ni3S2 is mediated by increased serum erythropoietin activity.

Animals↗
PubMed1979

Induction of sarcomas in nude mice by implantation of Syrian hamster fetal cells exposed in vitro to nickel subsulfide.

In vitro exposure of Syrian hamster fetal cells to nickel subsulfide (alpha Ni3S2) yielded positive colony assays for morphological transformation. A dose-response relationship was found between the concentration of alpha Ni3S2 and the incidence of morphological transformation. Exposures of alpha Ni3S2 induced morphological transformation at concentrations (0.1 or 1.0 microgram/ml of culture medium) which did not impair cell plating efficiency. Nickel monosulfide (NiS) did not induce morphological transformation of Syrian hamster fetal cells under the same conditions. Clones of alpha Ni3S2-transformed cells were able to grow in soft agar medium and demonstrated increased basal and induced activities of ornithine decarboxylase. Undifferentiated sarcomas developed in 26 of 27 nude mice at the site of s.c. injection of clones of alpha Ni3S2-transformed cells. No tumors developed in 19 control nude mice which were given s.c. injections of nontransformed Syrian hamster fetal cells which had not been exposed to alpha Ni3S2. This study demonstrates that fetal cells which undergo transformation following exposure to alpha Ni3S2 are capable of producing malignant tumors in nude mice.

Animals↗
PubMed1978

Induction of testicular sarcomas in Fischer rats by intratesticular injection of nickel subsulfide.

Nickel subsulfide (Ni3S2) was injected in various amounts into the testis of adult Fischer rats for the study of the acute and chronic effects of Ni3S2 on testicular cells. Rats given injections of 0.6 to 10 mg of Ni3S2 developed an immediate inflammatory response at the site of injection, followed by a delayed, slowly evolving coagulation necrosis of seminiferous tubules and interstitial cells. The extent of testicular necrosis was dose dependent, but at doses of 5 or 10 mg of Ni3S2 the rats invariably developed subtotal destruction of the testis. The testis became atrophic, without regeneration of seminiferous tubules. No damage was seen in the other testis, and no systemic effects were noted. Malignant testicular neoplasms developed in 16 of 19 rats within 20 months after an injection of 10 mg of Ni3S2. These neoplasms were classified by light and electron microscopy as fibrosarcomas, malignant fibrous histiocytomas, and rhabdomyosarcomas. None of the testicular neoplasms was derived from germ cells or genital cord cells. The occurrence of rhabdomyosarcomas in the testis, an organ normally devoid of striated muscle, suggests that Ni3S2 induces malignant transformation of undifferentiated, pluripotential mesenchymal cells.

Animals↗
PubMed1978

Interlaboratory comparisons of nickel analyses in urine by atomic absorption spectrometry.

Two interlaboratory surveys of urine nickel analyses were performed in which eight or nine urine samples were distributed to laboratories in seven nations for measurements of nickel concentrations by atomic absorption spectrometry. In both surveys, wide discrepancies were observed in the values for urine nickel concentrations that were obtained in different laboratories by various analytical methods. This finding documents a serious need for improvement in the proficiency of nickel analyses. Nonetheless, excellent interlaboratory concordance was found in the rankings of urine samples in order of increasing nickel concentrations. Analytical techniques that involved preliminary wet or dry ashing and extration steps before flameless atomic absorption spectrometry were generally superior to techniques for direct analysis of urine by flameless atomic absorption spectrometry in respect to (a) analytical sensitivity, (b) recovery of added nickel, (c) interlaboratory precision, and (d) interlaboratory concordance of ranking of urine samples in order of increasing nickel concentrations.

Evaluation Studies as Topic↗
PubMed1977

Carcinogenicity of nickel subsulfide in Fischer rats and Syrian hamsters after administration by various routes.

In an endeavor to expand the variety of experimental models for study of nickel carcinogenesis, nickel subsulfide (Ni3S2) was administered to rodents by five previously untested routes. In two groups of Syrian hamsters, Ni3S2 induced multiple sarcomas at the sites of single im injections (5 or 10 mg of Ni3S2). In contrast, Ni3S2 did not induce any malignant tumors of the cheek pouches, oral cavity or gastrointestinal tract, despite multiple local applications to the cheek pouches of several groups of hamsters in total dosages as large as 1.1 g of Ni3S2. In a group of Fischer rats, single intratesticular injections of Ni3S2 (10 mg) induced many testicular sarcomas. In contrast, no malignant tumors developed in two groups of rats that received single injections into the submaxillary gland (2.5 mg of Ni3S2) or into the liver (5 mg of Ni3S2 via the portal venous system).

Animals↗
PubMed1977

Comparisons of antidotal efficacy of sodium diethyldithiocarbamate, D-penicillamine and triethylenetetramine upon acute toxicity of nickel carbonyl in rats.

Sodium diethyldithiocarbamate, D-penicillamine, and triethylene-tetramine were administered to rats by im injection in dosages equivalent to 0.6 times their respective LD50 values in order to compare their relative effectiveness in prevention of death caused by exposure for 15 min to inhalation of nickel carbonyl (1.4 or 4.2 mg Ni (CO)4/liter of air). When the three drugs were administered to groups of rats at 10 min before or after the exposure to nickel carbonyl, sodium diethyldithiocarbamate was the most effective antidote. In contrast, then the drugs were administered at 6 hr after exposure to nickel carbonyl, D-penicillamine was the most effective antidote. Based upon the combined results of 4 sets of experiments, sodium diethyldithiocarbamate and D-penicillamine were significantly more effective than triethylenetetramine. The authors recommend that sodium diethyldithio-carbamate should remain the chelating agent of choice for therapy of nickel carbonyl poisoning. If sodium diethyldithiocarbamate is not available or if its use is contraindicated, D-penicillamine might be considered as an alternative chelating agent.

Animals↗
PubMed1977

Mechanisms of dissolution of nickel subsulfide in rat serum.

To elucidate the initial steps of carcinogenesis by nickel subsulfide, the mechanisms of dissolution of alpha-Ni3S2 were studied by incubating alpha-Ni3S2 dust in (a) water, (b) rat serum, and (c) rat serum ultrafiltrate. The sediments that remained following incubation of alpha-Ni3S2 in the 3 media for 2 weeks were examined by X-ray diffractometry. The rates of solubilization of 63Ni from alpha-63Ni3S2 during incubation in the 3 media were measured by liquid scintillation counting. These studies showed that solubilization of Ni(II) from alpha-Ni3S2 in rat serum requires the presence of O2 and involves three reactions: [I] 2 alpha-Ni3S2 + O2 + 2H2O leads to 4 beta-NiS + 2Ni(OH)2; [ii] beta-NiS + 202 leads to Ni2+ + SO4(2-); and [III] Ni2+ & Ni(OH)2 + serum ligands [albumin & amino acids] leads to soluble Ni(II)-complexes. The rate of solubilization of 63Ni from alpha-63Ni3S2 was initially more rapid in rat serum than in serum ultrafiltrate and much more rapid than in water. After 2 days of incubation the rates of dissolution of alpha-63Ni3S2 in the 3 media became progressively retarded, probably owing to deposition of insoluble surface coatings of beta-63Nis and 63Ni(OH)2 on the alpha-63Ni3S2 particles.

Air↗
PubMed1977

Furildioxime method for nickel analysis in serum and urine by electrothermal atomic absorption spectrometry.

We describe a method of analysis for nickel in serum and urine. After the sample (1 ml) has been subjected to acid digestion, Ni(II) is extracted into methylisobutylketone as a furildioximate complex, and is measured by electrothermal atomic absorption spectrometry. The method is more sensitive and more convenient than previous methods, and is less subject to nickel contamination because the digestion and extraction steps are performed in a single tube. Analytical recovery of Ni(II) (10 or 20 microng/liter) added to 20 specimens of serum or urine averaged 101% (range, 94 to 107). The following values (mean +/- SD) were obtained for nickel concentrations in specimens of serum and urine from 19 healthy adults living in central Connecticut: serum = 3.1 +/- 1.6 microng/liter; urine = 2.7 +/- 1.6 microng/liter. The method provides a practical means for monitoring occupational exposures of workers to nickel compounds.

Adult↗
PubMed1977

Inhibition by concanavalin A as the basis for a specific assay of serum 5'-nucleotidase activity.

Concanavalin A inhibits serum 5'-nucleotidase activity, without causing significant inhibition of alkaline phosphatase activity. This observation serves as the basis for a new method for assaying the 5'-nucleotidase activity in serum, which depends upon the difference between the enzymic hydrolysis of adenosine-5'-monophosphate in the presence and absence of concanavalin A. A denosine released by the 5'-nucleotidase reaction is deaminated by a coupled reaction with adenosine deaminase to liberate inosine and ammonia, and ammonia is measured colorimetrically by the Berthelot reaction. In sera from 40 healthy adult persons, 5'-nucleotidase activity averaged 6.4 U/liter (SD, +/-2.0; range, 3-12). In sera from 100 patients, measurements of 5'-nucleotidase activity by the new assay averaged 8% lower than by a generally accepted method in which phenyl phosphate is used to suppress hydrolysis of adenosine-5'-monophosphate by alkaline phosphatase activity. The clinical validy of the new assay was tested by measuring serum 5'-nucleotidase activities in rats with bile duct ligation and in rats treated with thioacetamide to induce hepatocellular injury.

Adult↗
PubMed1976

Effects of manganese on carcinogenicity and metabolism of nickel subsulfide.

Nickel subsulfide, Ni3S2, alone or combined with manganese or chromium dusts, was administered i.m. to Fischer rats to study the effects of the metals upon Ni3S2 induction of sarcomas at the injection site. The incidence of sarcomas within 2 years after injection of Ni3S2 (1.2 mg) plus manganese (1.0 mg) was 7%, versus 77% in rats that received only Ni3S2 (1.2 mg), and 80% in rats that received Ni3S2 (1.2 mg) plus chromium (1.0 mg) (p less than 0.005). No local sarcomas occurred in rats that received the injection vehicle, or in rats that received manganese or chromium without Ni3S2. Admixture of manganese diminished the solubility of 63Ni3S2 in rat serum, serum ultrafiltrate, or water, in vitro. Admixture of manganese with 63Ni3S2 did not affect the mobilization or excretion of 63Ni in vivo, nor did it alter the acute pathological reactions to Ni3S2. 63Ni concentrations in ultrafiltrates of supernatant fractions of homogenates of injection sites averaged 2.8 (S. D. +/- 0.7) ng/ml at 5 to 6 months after injection of 63Ni3S2 (1.2 mg) plus manganese (1.0 mg), versus 5.4 +/- 2.0 ng/ml after injection of only 63Ni3S2 (1.2 mg) (p less than 0.02). This study demonstrates that admixture of manganese dust and Ni3S2 inhibits Ni3S2 tumorigenesis in rats, and reveals that manganese dust affects the subcellular distribution of 63Ni derived from 63Ni3S2, without influencing 63Ni kinetics as estimated by compartmental analysis.

Animals↗