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PubMed1993

Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin.

The Polycomb group (Pc-G) proteins are responsible for keeping developmental regulators, like homeotic genes, stably and inheritably repressed during Drosophila development. Several similarities to a protein class involved in heterochromatin formation suggest that the Pc-G exerts its function at the higher order chromatin level. Here we have mapped the distribution of the Pc protein in the homeotic bithorax complex (BX-C) of Drosophila tissue culture cells. We have elaborated a method, based on the in vivo formaldehyde cross-linking technique, that allows a substantial enrichment for Pc-interacting sites by immunoprecipitation of the cross-linked chromatin with anti-Pc antibodies. We find that the Pc protein quantitatively covers large regulatory regions of repressed BX-C genes. Conversely, we find that the Abdominal-B gene is active in these cells and the region devoid of any bound Pc protein.

Animals↗
PubMed1987

General solution of the diffusion equation: application to formaldehyde sterilization and desorption of polymers.

A general solution of the diffusion equation for gas in polymers is developed by a numerical method. This solution allows diffusion to be calculated in all cases, by gas desorption after an incomplete adsorption, which is not the case for analytical solutions. When the analytical solutions are valid, both types of solution give identical results. The effect of equivalent sterilization treatment at different temperatures and gas concentrations on formaldehyde residuals in 9 polymers is calculated. High temperature gives lower residual content. Short sterilization times at high gas concentration produce a higher residual content at the end of the adsorption and a lower residual content during desorption than longer sterilization times with lower gas concentration. This is due to sharper gradients of diffusant in the polymer.

Chemical Phenomena↗
PubMed1995

Effect of formaldehyde fixation on some mechanical properties of bovine bone.

The risk of infection of investigators working on the biomechanics of human bone from a variety of modern pathogens including the human immunodeficiency virus or the hepatitis B virus has increased recently. New safety procedures are needed to reduce that risk. The procedure we follow in our laboratory employs brief (< 3 h) fixation in formaldehyde, and we report here the effects it has on some mechanical properties of bovine bone. Results in quasistatic loading tests were almost unaffected by our fixation protocol, but a significant decrease in impact strength was found. These results indicate that there may be some interaction between fixation and strain rate dependent effects and, therefore, some caution is needed when using common biomechanical measurement methods on fixed bone material.

Animals↗
PubMed1996

Formaldehyde mechanistic data and risk assessment: endogenous protection from DNA adduct formation.

Exposures of rodents to airborne formaldehyde (FA) produce dose-related toxicity, enhanced cell proliferation and squamous cell carcinomas in the nasal passages. The mechanism of FA-induced tumor formation involves DNA-protein crosslink formation and enhanced cell proliferation secondarily to cytotoxicity. The mucociliary apparatus and glutathione protect against low-dose FA-induced effects. Consequently, the mechanistic information is consistent with a very sublinear dose-response curve for tumor formation. The sublinear dose-response of nasal DNA-protein crosslinks levels in rodents and monkeys has been used in the risk assessment of FA.

Animals↗
PubMed1980

The aluminum-formaldehyde (ALFA) histofluorescence method for improved visualization of catecholamines and indoleamines. 2. Model experiments.

The fluorescence-promoting effects of sodium, magnesium and aluminum ions in the histochemical formaldehyde (FA) reaction with catecholamines and indoleamines have been studied in protein models. The positive effects of aluminum and magnesium salts on the monoamine fluorescence yields, seen in tissue, could partly be reproduced in a simple protein matrix. The fluorescence-promoting potency was greatest for aluminum, moderate for magnesium and small for sodium. The aluminum effect was markedly concentration-dependent, with an optimum at a concentration of 5-10 mM in the model solution. Optimum pH was around 3.8. Experiments with synthetic fluorophores indicate that the principal action of the metal ions is on the fluorescence properties of the monoamine fluorophores rather than on the yield of fluorophores in the reaction of the monoamines with FA. The presence of aluminum ions in the models thus causes both increases in the fluorescence efficiency of the fluorophores as well as changes in their spectral properties. The direct effects on the monoamine fluorophores cannot, however, account for all effects of the metal salts seen in tissue. It is suggested that aluminum and magnesium ions, in addition, can act as acid catalysts in the FA-monoamine reactions, and that the metal salts have a direct effect on the tissue environment, leading to a 'locking-in' of the intracellular monoamines.

Aluminum↗
PubMed1993

Four modified silver methods for thick sections of formaldehyde-fixed mammalian central nervous tissue: 'dark' neurons, perikarya of all neurons, microglial cells and capillaries.

Four reliable silver methods for the visualization of acute or advanced phases of neuronal damage have been modified so that they can be performed with good results on materials freshly fixed with transcardial perfusion of buffered formaldehyde for other silver methods and immunocytochemical techniques. The four modified methods respectively stain: (1) the somata and dendrites of 'dark' (impaired) neurons, (2) the perikarya of all neurons, (3) microglial cells, and (4) capillaries. Without the present modifications the 'dark' neuron method is only effective with glutaraldehyde fixation while the other three methods predominantly stain myelin in freshly fixed mammalian nervous tissue.

Animals↗
PubMed1994

Effects of microwave pretreatment on immunocytochemical staining of vibratome sections and tissue blocks of human cerebral cortex stored in formaldehyde fixative for long periods.

The effects of the microwave antigen-retrieval method were investigated for five antibodies commonly used in neurosciences, i.e., Parvalbumin, Calbindin D28-K, MAP-2, MAP-5 and SMI-32. Immunocytochemical stainings were performed on free-floating vibratome sections of tissue which had been stored in fixative for as long as 10 months to compare the effects of microwave treatment in one of the different metal solutions or in distilled water. Microwave treatment of free-floating vibratome sections led to a severe wrinkling of the sections. Therefore the possibility of pretreatment of a thick tissue slice before vibratome sectioning was investigated. We conclude that microwave pretreatment of tissue slices in an aluminium chloride solution is the preferable antigen-retrieval procedure for the examined antibody staining when the immunocytochemical staining is lost or markedly reduced after storage in formaldehyde fixative for a long period. In particular SMI-32 and MAP-2, but also Parvalbumin staining, improved enormously after such a pretreatment.

Adult↗
PubMed1981

Genetic effects of formaldehyde in the mouse.

A chromosomal analysis of spermatocytes at metaphase I failed to reveal any chromosomal lesions during spermatogenesis of mice treated with formaldehyde. Similarly, the dominant lethal test, except during the first and third weeks, showed no detectable effect.

Animals↗
PubMed1983

Evaluation of some formaldehyde-release compounds and other biocides in the mouse micronucleus test.

A number of biocidal chemicals were tested for clastogenic activity in the micronucleus test using C57Bl/6J mice. The materials tested were: 5-chloro-2-methyl-4-isothiazolin-3-one (I), N-methyl-isothiazolone hydrochloride (II), Glokill 77 and Parmetol A23. Two of the biocides (Glokill and Parmetol) depend on the release of formaldehyde for their activity while the other two compounds are the active chemicals in the biocide Kathon. Hexamethylphosphoramide (HMPA) was tested as the positive control for the series and N,N-dinitrosopentamethylenetetramine (DNPT) as the negative control. HMPA produced significant dose-related increases in the incidence of micronuclei whereas DNPT, I, II, Glokill and Parmetol A23 were without effect.

Animals↗
PubMed1985

Cytogenetic effects in lymphocytes of formaldehyde workers of a paper factory.

Chromosome analyses were carried out in lymphocytes from 20 male papermakers exposed to formaldehyde (FA) for 2-30 years. 20 male workers from the same factory but without FA exposure served as controls. In the exposed group a significantly increased incidence of dicentrics or dicentrics and ring chromosomes was observed for 11 workers currently employed as supervisors. In contrast to 9 operators their total mean exposure time to FA was about 2.5 times longer. No significantly higher SCE values were found for smoking or for non-smoking FA workers compared with the corresponding control subjects.

Adult↗
PubMed1988

Direct analysis of the clastogenic effect of formaldehyde in unstimulated human lymphocytes by means of the premature chromosome condensation technique.

The cytogenetic effect of formaldehyde (FA) on unstimulated human lymphocytes was studied by means of conventional chromosome analysis and the premature chromosome condensation (PCC) technique. In first post-treatment metaphases no significantly increased yields of chromosomal changes could be observed. The analysis of PCCs, however, showed high yields of chromosome fragments. Bleomycin (BLM) used as positive control was also highly clastogenic in PCCs and resulted in significantly increased yields of chromosome-type aberrations. As recently argued, a premitotic selection against heavily damaged cells could be an explanation for the discrepancy between the chromosome findings in metaphase and PCC analysis after FA treatment. In addition, a differential effectiveness may exist in unstimulated lymphocytes to convert multiple fragmentation into chromatid- or chromosome-type aberrations through S-phase-dependent or S-phase-independent mechanisms.

Animals↗
PubMed1983

Induction of cytogenetic effects in human fibroblast cultures after exposure to formaldehyde or X-rays.

Cytogenetic changes induced by formaldehyde (FA) in exponentially growing human fibroblasts were compared with those produced by X-rays. Chromosome aberrations of different types were detected. Exposure to 2 mM FA for 15 min resulted, quantitatively and qualitatively, in effects comparable to those produced by an X-ray dose of 100 rad. X-Rays at higher exposures produced types of chromosome aberrations that differed from those induced by higher exposures to FA.

Cells, Cultured↗
PubMed1990

13C-NMR of Clostridium pasteurianum ferredoxin after reductive methylation of the amines using [13C]formaldehyde.

Clostridium pasteurianum 2(4Fe-4S) ferredoxin has been reductively methylated using [13C]formaldehyde and sodium cyanoborohydride. Lys3 and the N-terminal alanine, the only amines in the protein, are both dimethylated by this procedure. 13C-NMR titration of the apo, oxidized and reduced modified ferrodoxin indicate that the lysine pK is slightly over 10 in all three forms of the protein. In contrast, the N-terminal alanine shifts from a pK of 7.7 in the apoprotein to greater than 9 in both the oxidized and reduced modified ferredoxin. The unexpectedly high pK observed for the N-terminus is consistent with the presence of an ion pair in both the oxidized and reduced native forms of the protein. The methylated ferrodoxin is considerably less stable than the native protein, indicating an important role for the amines in protein stability.

Amines↗
PubMed1988

High sensitivity towards monensin of receptor-mediated endocytosis of formaldehyde treated albumin by liver endothelial cells.

Endocytosis of formaldehyde-treated serum albumin (f-albumin) in isolated liver sinusoidal endothelial cells was studied. Uptake occurs via the scavenger receptor and was found to be very sensitive to the ionophore monensin. Binding at 4 degrees C of f-albumin was reduced to 50% of control values by preincubation for 2 min with 2 microM monensin. Both uptake and degradation of f-albumin were more sensitive to monensin. No lag-phase in the inhibitory effect on uptake and degradation was detected. A concentration of 0.1 microM monensin reduced uptake of f-albumin by 50%. Degradation of internalized f-albumin was reduced by 50% in the presence of 0.2 microM monensin. Since uptake and degradation of f-albumin were very sensitive to monensin, the effect of introducing the drug during endocytosis of the ligand was tested. All processing of f-albumin stopped instantly upon addition of monensin; hence, there seems to be no step in the endocytic process beyond which monensin is ineffective. The data suggest that the scavenger receptor of liver endothelial cells is internalized and recycled very rapidly.

Animals↗
PubMed1988

A review of regulatory risk assessment with formaldehyde as an example.

Quantitative risk assessment may vary by over a millionfold depending upon the model used. The EPA currently uses models which project the highest potential risk. Furthermore, there is no consideration of the probability that a chemical is a human carcinogen. Such an approach may result in unrealistically high risk at exposures far below current ambient levels. In the case of formaldehyde, three alternative approaches to risk assessment are examined. One uses the maximum likelihood estimate of the multistage model, another uses the no observable adverse effect level divided by a safety factor of 100, and the third uses a probability estimate that the substance is carcinogenic at typical ambient exposures multiplied by EPA's upper bound estimate. The probability estimate is made from considerations of metabolism and pharmacokinetics, toxicology, short-term tests, animal tests, and epidemiology.

Animals↗
PubMed1983

Toxicological evaluation in rats and mice of the ingestion of a cheese made from milk with added formaldehyde.

Male Swiss albino mice (CD-1) and male Sprague-Dawley rats were given single oral doses of 0.5 g (4.0 microCi) and 2.2 g (18 microCi) 14C-labelled grana cheese, respectively. The cheese was made by the normal process but using milk with added [14C]formaldehyde. The plasma and tissue kinetics of the radiolabelled cheese were studied by monitoring the decay of radioactivity in the plasma, gastrointestinal tract, liver, kidney, lung, testes, spleen, brain, muscle and adipose tissue. The faeces and urine of animals placed in individual metabolism cages were collected between 4 and 64 hr after dosing for rats and between 2 hr and 12 days for mice. Within 32 hr of administration 63-67% of the radioactivity had been excreted in the faeces and urine and 24-28% of the radioactivity had been exhaled as 14CO2, in both species. Maximum concentrations, corresponding to 0.07% and 0.3% of the dose per ml of blood were reached respectively within 8 hr for rats and 2 hr for mice. The toxicokinetic profile appears to be similar in mice and rats because of the similarity of the half-lives of the elimination phase, 27.8 and 26.4 hr respectively, and suggests that accumulation of the 14C-activity does not occur in any of the tissues of either species. The low levels of radioactivity still present 32 hr after the administration of 14C-grana cheese are probably due to the residues of labelled fractions of milk protein not completely metabolized.

Amino Acids↗
PubMed1988

Formaldehyde concentrations in the blood of rhesus monkeys after inhalation exposure.

The effect of subchronic exposure to formaldehyde (HCHO; 6 ppm; 6 hr/day, 5 days/wk for 4 wk) on the HCHO concentration in the blood of three rhesus monkeys was investigated. Immediately after the final exposure, the monkeys were sedated, and blood samples were withdrawn 7 min after the end of exposure. The HCHO concentration in the blood, determined by gas chromatography-mass spectrometry was 1.84 +/- 0.15 micrograms/g blood and did not differ significantly after a further 45 hr without exposure to HCHO (2.04 +/- 0.40 micrograms/g blood). The average concentration of HCHO in the blood of exposed monkeys was also not significantly different from that of three unexposed controls (2.42 +/- 0.09 micrograms/g blood). However, individual monkeys differed significantly from one another with respect to their blood concentrations of HCHO. These results indicate that subchronic inhalation exposure of non-human primates to HCHO has no significant effect on the HCHO concentration in the blood, and that the average concentration of HCHO in the blood of monkeys is similar to that in the blood of humans.

Administration, Inhalation↗
PubMed1982

Formaldehyde and tumors in hamster respiratory tract.

Male Syrian golden hamsters were exposed to 10 ppm of formaldehyde (H2CO) 5 times/week for lifetime. Survival of the treated animals was reduced relative to unexposed controls. No tumors were observed in histologic sections of respiratory tract tissues from either unexposed or treated animals. Only a minimal increase in hyperplastic and metaplastic areas was observed in nasal epithelium of exposed animals. However, there was evidence that H2CO could serve as a cofactor in the incidence of respiratory tumors induced by diethylnitrosamine (DEN). Animals were exposed once per week to 30 ppm H2CO (5 h/day) for lifetime. No tumors were observed in the respiratory tract of the H2CO-only control group exposed to this regimen. Hamsters receiving exposures to H2CO at 2 days prior to each of 10 weekly DEN injections had a higher number of tracheal tumors/tumor-bearing animal at autopsy than those receiving DEN alone.

Adenoma↗