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PubMed1977

3H estradiol in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence.

3H setradion-17beta was localized in nuclei of catecholamine (CA) neurons of the rat lower brain stem, i.e., midbrain, pons and medulla, by employing a combined formaldehyde-induced fluorescence (FIF)-autoradiography approach which permits the direct visualization of 3H estradiol uptake in relation to CA-neuron perikarya and terminals. In the medulla, noradrenalin (NA)-containing neurons in and adjacent to the nucleus (n.) reticularis lateralis (group A1) and in the vicinity of the n. tractus solitarii (group A2) concentrated 3H estradiol. In the pons, NA neurons dorsal to the n. olivaris superior (group A5), in the locus ceruleus (group A6) and ventral to the pedunculus cerebellaris superior (group A7) displayed 3H estradiol uptake. In the midbrain, dopamine (DA)-containing neurons in the n. cuneiformis (group A8), in the zona compacta of the substantia nigra (group A9) and adjacent to the n. interpeduncularis (group A10), were not seen to concentrate 3H estradiol. This is in contrast to DA neurons in the n. arcuatus of the hypothalamus (group A12), previously reported to concentrate 3H estradiol. In addition, certain non-CA-containing neurons with nuclear uptake of 3H estradiol were observed to be surrounded by CA terminals in such areas as substantia grisea centralis, n. tractus solitarii and n. tractus spinalis nervi trigemini. This suggests a second mode of interaction between CA neurons and estrogen target neurons. The estradiol-CA neuron relationships described may provide morphological substrates underlying functional interactions between estradiol and CA neurons in the rat brain.

Animals↗
PubMed1981

(3-H)-dihydrotestosterone in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence.

A combined formaldehyde-induced fluorescence (FIF)-autoradiography procedure was used to determine how and where the androgen, dihydrotestosterone (DHT), is associated with catecholamine systems in the rat brain. With this dual localization method, (3H)-DHT target sites can be visualized in relation to catecholamine perikarya and terminals. In the hindbrain, catecholamine neurons adjacent to the fourth ventricle (group A4), the nucleus (n.) olivaris superior (group A5), the n. parabranchialis medialis (group A7), and in the locus coeruleus (group A6) and subcoeruleal regions, as well as in the substantia grisea centralis, concentrate (3H)-DHT in their nuclei. (3H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following hindbrain regions: n. motorius dorsalis nervi vagi, n. tractus solitarii, n. commissuralis, n. raphe pallidus, n. olivaris inferior, the ventrolateral portion of the substantia grisea centralis, n. cuneiformis, and the ventrolateral reticular formation in the caudal mesencephalon. In the forebrain, (3H)-DHT concentrates in nuclei of catecholamine neurons located in the n. arcuatus and n. periventricularis (group A12). In addition, (3H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following forebrain regions: n. periventricularis rotundocellularis, n. paraventricularis, n. dorsomedialis, n. periventricularis, area retrochiasmatica, n. interstititalis striae terminalis (ventral portion), and n. amygdaloideus centralis. The disclosure of a morphologic association between (3H)-DHT target sites and certain brain catecholamine systems suggests a close functional interdependence between androgens and catecholamines.

Animals↗
PubMed2006

Development of a capillary electrophoresis-mass spectrometry method for the determination of formaldehyde releasers as their hydrolysis products and amino alcohols from metal working fluids.

Metal working fluids (MWFs) are widely used as lubricants and coolants for different industrial operations. Biocides are ingredients of MWFs to control the microbial growth; derivatives of hexahydrotriazines and oxazolidines are generally used. Because of the lack of appropriate characterization, an existing capillary electrophoretic method for their quantification was improved. During the process of optimization, it became clear that hydrolysis products, derivatives of amino alcohols, severely interfere with the separation procedure. Since indirect-UV detection lacked the required selectivity, mass-selective detection was employed. NMR and MS established the absence of amino alcohols in the original educts. The aqueous solutions of the biocides stored for extended time remained amino alcohol-free, suggesting that these amino alcohols are formed from the biocides during the capillary electrophoretic separation. The observation of narrow and symmetric peaks indicated hydrolysis, and the polarity of the products implied favorable conditions for capillary electrophoretic separation. Methods were optimized for the analysis of the amino alcohols, the hydrolytic products of the formaldehyde releasers, using indirect-UV and MS detection. This method was extended to other likely solutes used as alkaline-reserve ingredients. The analytes were separated within 9 min with a high precision of migration times (the RSDs were below 1.5%). When quantifying from mobility scale, the calibration curves produced linearity with regression coefficients in the range of 0.990-0.999. The detection limit was lower than 1 mg/L in the case of MS detection. The influence of water-based MWF was also investigated, and no matrix effect on the migration of the analytes and on the peak areas was observed.

Amino Alcohols↗
PubMed1986

Formaldehyde-induced acentric chromosome fragments and chromosome stickiness in Chortophaga neuroblasts.

Embryos of the grasshopper Chortophaga viridifasciata were exposed in vitro to formaldehyde (FA), as formalin, at concentrations ranging from 10(-8)M (0.0003 ppm) to 10(-3) M (30 ppm) at 38 degrees C. A low frequency of distinct acentric chromosome fragments (0.02-0.04/cell) was observed in the neuroblasts after 1 hr exposure to 7.5 X 10(-4) or 10(-3) M FA plus 3 hr recovery, but not at lower concentrations, even with 4 hr exposure. There was no obvious relation between distinct fragment frequency and concentration of FA. Neuroblasts with sticky chromosomes were observed at 10(-4), 7.5 X 10(-4), and 10(-3) M FA, the percent of cells with slight, moderate, or severe stickiness varying with FA concentrations. Fragments were associated with the sticky chromosomes. The frequency of these sticky fragments at the two higher concentrations (0.15-0.30/cell) was greater than the frequency of distinct fragments. It is concluded that the distinct acentric fragments induced by FA result from breakage at a single sticky point (slight stickiness) between separating sister chromatids. The chromosome effects observed probably result from the action of daughter products that are formed by the interaction of FA with culture medium components, especially the fetal calf serum.

Animals↗
PubMed1988

Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli.

The molecular nature of formaldehyde (HCHO)-induced mutations was studied in both human lymphoblasts and E. coli. Thirty HPRT- human lymphoblast colonies induced by eight repetitive 150 microM HCHO treatments were characterized by Southern blot analysis. Fourteen of these mutants (47%) had visible deletions of some or all of the X-linked HPRT bands, indicating that HCHO can induce large losses of DNA in human lymphoblasts. In E. coli, DNA alterations induced by HCHO were characterized with use of the xanthine guanine phosphoribosyl transferase (gpt) gene as the genetic target. Exposure of E. coli to 4 mM HCHO for 1 hr induced large insertions (41%), large deletions (18%), and point mutations (41%). Dideoxy DNA sequencing revealed that most of the point mutations were transversions at GC base pairs. In contrast, exposure of E. coli to 40 mM HCHO for 1 hr produced 92% point mutations, 62% of which were transitions at a single AT base pair in the gene. Therefore, HCHO is capable of producing different genetic alterations in E. coli at different concentrations, suggesting fundamental differences in the mutagenic mechanisms operating at the two concentrations used. Naked pSV2gpt plasmid DNA was exposed to 3.3 or 10 mM HCHO and transformed into E. coli. Most of the resulting mutations were frameshifts, again suggesting a different mutagenic mechanism.

Chromosome Deletion↗
PubMed1994

PCR-RFLP studies on chromosome 3p in formaldehyde-fixed, paraffin-embedded cervical cancer tissues.

Loss of heterozygosity (LOH) has been extensively studied on the short arm of chromosome 3, and functional proofs have been obtained defining a tumor-suppressor locus at 3p21-22. We examined 31 paraffin-embedded cervical cancer samples for LOH, using 5 PCR-primer pairs, located around 3p21. Allele loss was found in 19 out of the 27 informative samples (70%) while 13 out of 23 informative samples (56%) had LOH located at 3p21-22. More of the human papillomavirus (HPV)-positive samples had LOH compared to the HPV-negative samples, giving only a weak association between loss of allele and HPV integration. Modifications of the DNA in the formaldehyde-fixed samples were detected, and further studies will be required to clarify how such artifacts may affect restriction fragment length polymorphism (RFLP) studies on fixed tissues.

Alleles↗
PubMed1983

The health hazards of formaldehyde.

Formaldehyde is ubiquitous in the environment. As an aqueous solution, it causes burns on contact with the skin and eyes, and the vapour is irritating to the eyes and respiratory system. It is a sensitizing agent and may affect susceptible individuals at levels below the current British TLV of 2 ppm. It has been tested for teratogenicity in several animal species by a variety of routes, but was not positive in any of the studies. Inhalation of the vapour has been shown to cause nasal cancer in rats and mice. However, epidemiological studies have failed to confirm whether or not the compound is carcinogenic in humans.

Animals↗
PubMed2002

Induction of c-fos and c-jun protooncogenes expression by formaldehyde-releasing and epoxy resin-based root-canal sealers in human osteoblastic cells.

An important requirement for a root-canal sealer is biologic compatibility; most evaluations have focused on general toxicological and local tissue irritating properties. There is only scant information about mutagenicity or carcinogenicity testing for root-canal sealer. It has been shown that c-fos and c-jun are induced rapidly by a variety of chemical and physical stimuli. Numerous works have extensively investigated the induction mechanisms of c-fos and c-jun protooncogenes by these agents; however, little is known about the induction of cellular signaling events and specific gene expression after cell exposure to root-canal sealers. Therefore, we used osteoblastic cell line U2-OS to examine the effect of zinc-oxide eugenol-based (N2 and Endomethasome), epoxy resin-based (AH Plus), and calcium hydroxide-based (Sealapex) root-canal sealers on the expression of c-fos and c-jun protooncogenes to understand in more detail the molecular mechanisms of root-canal sealer-induced genotoxicity. The cytotoxicity decreased in an order of N2 > Endomethasome > AH Plus > Sealapex. In addition, N2, Endomethasome, and AH Plus rapidly induced c-jun and c-fos mRNA levels in cells. However, Sealapex did not induce c-jun and c-fos mRNA expression at detectable levels all time points. Taken together, persistent induction of c-jun and c-fos protooncogenes by formaldehyde-releasing and epoxy resin-based root-canal sealers may be distributed systemically via apex to cause some unexpected adverse effects on human beings. These data should be taken into consideration when choosing a root-canal sealer.

Biocompatible Materials↗
PubMed1991

Prevention of bioprosthetic heart valve tissue calcification by charge modification: effects of protamine binding by formaldehyde.

Calcification is the principal cause of the clinical failure of bioprosthetic heart valves (BHV). Calcification occurs through an interaction of host and implant factors, mainly younger age and glutaraldehyde pretreatment, respectively. The hypothesis of this work was that an impaired balance between positively and negatively charged amino acids, due to the reaction with Lys and Hyl tissue-collagen residues, expose affinity sites to Ca++. We further hypothesized that regardless of the cause(s) of BHV calcification, positive charge modification of the tissues will prevent their propensity to calcify. Modification of BHV tissue was obtained by covalently binding protamine sulfate, a polybasic peptide, via formaldehyde and subsequent glutaraldehyde tissue crosslinking. Protamine-bound tissue exhibited stability properties (shrinkage temperature and resistance to collagenase digestion) similar to BHV tissue. Protamine-treated tissue was less permeable to Ca++, and reduced staining was observed with positively charged dyes, indicating the presence of positively charged functional groups in the modified tissue. Significant prevention of calcification was exhibited by the p-bound tissue in comparison to BHV tissue, 30.9 and 109 micrograms/mg calcium, respectively, after 30 days of subdermal implants in rats. The modification procedure resulted in stable, covalent links of approximately 10% w/w protamine with undiminished anticalcification properties, even after 1 year storage. The results support our hypotheses, and orthotopical heart valve replacements are required in order to completely evaluate the treatment efficacy and biocompatibility.

Biocompatible Materials↗
PubMed1993

Effects of carbon tetrachloride, menadione, and paraquat on the urinary excretion of malondialdehyde, formaldehyde, acetaldehyde, and acetone in rats.

Excretions of the lipid peroxidation products, formaldehyde (FA), acetaldehyde (ACT), malondialdehyde (MDA), and acetone (ACON), were simultaneously identified and quantitated in the urine of female Sprague-Dawley rats by gas chromatography-mass spectroscopy (GC-MS) and high pressure liquid chromatography (HPLC) following the acute administration of carbon tetrachloride, a model alkylating agent that does not induce glutathione depletion, and the redox cycling compounds paraquat and menadione. All three xenobiotics are well-known inducers of oxidative stress. Oxidative stress was induced by oral administration of single doses of 2.5 mL of carbon tetrachloride/kg, 60 mg menadione/kg, and 75 mg paraquat/kg. These doses are approximately 50% of the LD50's for the three xenobiotics. Urinary excretion of FA, ACT, MDA, and ACON increased relative to control animals following treatment with all xenobiotics. Over the 48 hours of the study, the greatest increases in the excretion of MDA, FA, ACT, and ACON occurred after paraquat administration, with increases of approximately 2.7-, 2.6-, 4.3-, and 11.0-fold, respectively. This technique may have wide-spread applicability as an effective biomarker for investigating altered lipid metabolism in disease states and exposure to environmental pollutants/xenobiotics.

Acetaldehyde↗
PubMed2001

Formaldehyde production by Tris buffer in peptide formulations at elevated temperature.

This technical note provides evidence for the degradation of Tris buffer in a peptide formulation stored at elevated temperature (70 degrees C). The buffer degrades to liberate formaldehyde, which is shown to react with the peptide tyrosine residue. Those involved in peptide/protein formulation should be aware of the possible instability in this common biological buffer.

Formaldehyde↗
PubMed1975

Colorimetric determination of formaldehyde via free radical formation.

Aliphatic aldehydes react with 2,3-dimethyl-2,3-bis-(hydroxylamino)butane and sodium periodate for form colored free radicals. These radicals were stabilized with pyridine in aqueous solution. Low levels of formaldehyde in aqueous solutions were determined utilizing this reaction.

Colorimetry↗
PubMed2001

One hundred consecutive treatments with holmium: YAG laser for pulmonary bullae: especially in conjunction with gelatin-resorcinol formaldehyde-glutaraldehyde glue adhesion.

BACKGROUND AND OBJECTIVE: We have widely used a Ho:YAG laser to treat bullae thoracoscopically. STUDY DESIGN/MATERIALS AND METHODS: Bullae with broad necks were treated with a Ho:YAG laser thoracoscopically. Because one patient relapsed after application of fibrin glue in the early period, a DEXON (polyglycolic acid) mesh patch soaked in fibrin glue was used through a 2-cm opening in the subsequent cases. Lastly, gelatin-resorcinol formaldehyde-glutaraldehyde (GRFG) glue was applied through a 5-mm opening instead of a DEXON mesh after coagulation. RESULTS: In the 38 patients patched with DEXON mesh soaked in fibrin glue and 56 patched with GRFG glue after coagulation, none relapsed. CONCLUSION: Combined uses of fibrin glue plus DEXON mesh or GRFG glue were effective when bullae were treated with the Ho:YAG laser. However, the wound was smaller and more cosmetic in the GRFG glue group than in the DEXON mesh plus fibrin glue group.

Blister↗
PubMed1994

Characterization of cell lines derived from formaldehyde-induced nasal tumors in rats.

Cell lines derived from formaldehyde-induced nasal tumors in Fischer 344 rats were established. All of the lines were found to be epithelial and aneuploid and to express keratin, transforming growth factor-alpha, and epidermal growth factor receptor transcripts. Two of four lines were tumorigenic upon injection into nude mice, and these lines also contained point mutations in the p53 suppressor gene. The data indicate that these lines possess characteristics that make them a valuable tool for the study of chemically induced respiratory tract carcinogenesis.

Animals↗
PubMed1990

Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase.

An avidin-biotin enhanced immunoperoxidase procedure using monoclonal antibodies (AA1, AA3, and AA5) prepared against human mast cell tryptase resulted in intense staining of mast cells in paraffin-embedded tissue. The distribution of mast cells observed was similar to that seen when adjacent serial sections were stained using a standard procedure with toluidine blue, though the immunoperoxidase technique permitted the identification of significantly more mast cells. With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary. There was no staining of antibody on basophils or on any other normal blood leukocyte. The technique was effective with tissue fixed in either Carnoy's or neutral buffered formalin, though the internal mast cell structure was better preserved with formaldehyde fixation. The immunoperoxidase staining procedure with monoclonal antibody AA1 is a highly specific and sensitive means for the detection of mast cells in routinely processed tissues.

Antibodies, Monoclonal↗
PubMed1993

Vector YFRp1 allows transformant selection in Saccharomyces cerevisiae via resistance to formaldehyde.

Formaldehyde (FA), a chemical with low toxic potential, is used as sole selective agent for transformation in the yeast Saccharomyces cerevisiae. Neither stable auxotrophic markers in recipient cells nor defined synthetic media are needed when multicopy vector YFRp1, containing the yeast SFA gene, is employed for yeast transformation. The SFA gene gives stability to the vector and its yeast (and other) passenger genes when transformants are propagated in complex media supplemented with 3-5 mM-FA. Use of inexpensive FA and non-synthetic, undefined media will lower the cost of yeast transformant propagation considerably and thus make feasible large-volume industrial application of transformants containing YFRp1 derivatives.

Drug Resistance, Microbial↗
PubMed1999

Identification of a chemical marker of environmental exposure to formaldehyde.

Formaldehyde (F) binds human serum albumin (HSA) covalently, giving rise to a molecular adduct F-HSA having the F as hapten. The humoral immune response to the adduct provides a biological marker of F exposure. In order to titrate serum anti-F-HSA antibodies, a new indirect competitive enzyme immunoassay (displacement assay) was developed. Two groups of about 90 heterogeneous healthy subjects were examined using two in vitro conjugated F-HSA adducts with different ratios between F and HSA (5:1 and 10:1). Contingency table analysis showed a greater sensitivity (97%) and specificity (92%) of the test with the 10:1 F-HSA adduct than with the 5:1. Data examination using multivariate analysis of variance revealed that in both groups the smoking variable significantly explains (P<0.01) the values of the F exposure marker. A significant association with immunological response was obtained only in male smokers, using 5:1 F-HSA adduct, while with 10:1 ratio, a good association in male and female smokers was found. Results confirm that the immunological assay developed (displacement assay) could be a useful method for evaluating F exposure, especially for public health monitoring on a large scale.

Adult↗
PubMed1994

DNA-protein cross-links and cell replication at specific sites in the nose of F344 rats exposed subchronically to formaldehyde.

Chronic exposures to high concentrations (> or = 6 ppm) of formaldehyde (HCHO) induce cell proliferation, squamous metaplasia, and squamous cell carcinomas in F344 rats. To assess the cancer risk associated with HCHO exposure, DNA-protein cross-links (DPX) formed in a single exposure of naive (previously unexposed) rats and monkeys have been used as a surrogate for the internal dose. Since the quantity of DPX may differ in subchronically exposed animals, the effects of preexposure to HCHO on the acute DPX yield (concentration of DPX following a single exposure) and the cumulative DPX yield (concentration of DPX following repeated exposures) were determined. Male F344 rats were preexposed (PE) to 0.7, 2, 6, or 15 ppm of HCHO (6 hr/day, 5 days/week, 11 weeks + 4 days). Naive (N) rats were exposed to room air. On the 5th day of the 12th week, PE and N rats were simultaneously exposed (3 hr) to H14CHO at the same concentrations used for preexposure. Acute DPX yields and cell replication (incorporation of 14C into DNA) were determined in the mucosal lining of the nasal lateral meatus (LM) (high tumor site in HCHO bioassay) and the medial and posterior meatuses (M:PM) (low tumor site in bioassay). DPX yields in the LM were approximately sixfold higher than in the M:PM. At 0.7 and 2 ppm, no differences between PE and N rats were detected in either tissue. At 6 and 15 ppm, acute DPX yields in the LM of PE rats were approximately half those of N rats, but no differences were detected in the M:PM. Cell proliferation was induced in PE rats at 6 ppm (LM only) and especially at 15 ppm (LM and M:PM). Cumulative DPX yields were measured indirectly by determining the decrease in extractability of DNA from proteins. PE rats were preexposed to 6 or 10 ppm as above, while N rats were exposed to room air. Both groups (PE and N) were then exposed (3 hr) to the same concentration of unlabeled HCHO. DPX yields increased in a concentration-dependent manner in both groups, but the yields were smaller in PE than N rats, suggesting that no accumulation of DPX occurred in PE rats. The results demonstrate that at concentrations < or = 2 ppm, N and PE rats are equivalent with respect to the formation of DPX.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗