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Biomedical subjects

D Wild

Publications and source records attributed to D Wild.

At least 73 records · Page 4Linked to original sources

Mutagenicity of the mercapturic acid and other S-containing derivatives of hexachloro-1,3-butadiene.

The main metabolic pathway of the genotoxic environmental contaminant hexachloro-1,3-butadiene (HCBD) is the direct conjugation reaction with glutathione. To establish structure-effect relationships we studied the mutagenic activity of four S-containing HCBD conjugates with and without metabolic activating enzymes (S9 mix) in Salmonella typhimurium. The N-acetyl-S-pentachlorobutadienyl-L-cysteine (mercapturic acid) was clearly mutagenic after metabolic activation; its mutagenic activity was 48.6 revertants/micrograms or 18.7 revertants/nmol, which is, on a molar basis, a mutagenic response 80 times greater than that of the parent compound HCBD. The mutagenic effect of the mercapturic acid rather decreased by addition to the pre-incubation system of pyridoxal 5'-phosphate, a co-factor of the enzyme beta-lyase. Methyl-N-acetyl-S-pentachlorobutadienyl-D,L-homocysteinate, structurally closely related to mercapturic acid, exerted a weak mutagenic effect comparable to that of HCBD. The two S-containing HCBD metabolites (S-pentachlorobutadienyl-mercaptoacetic acid and pentachlorobutadienyl-methylthioether) did not reveal significant mutagenic effects. The results indicate the involvement of the enzyme N-deacetylase which catalyzes the conversion of mercapturic acid to the HCBD-cysteine conjugate. In addition a high substrate specificity of the C-S bond-cleaving enzyme beta-lyase was observed.

Acetylcysteine↗

Mutagenic activity in rat urine after feeding with the azo dye tartrazine.

The azo dye tartrazine, after dosing by gavage, is transformed by rats into urinary metabolites which exert dose-dependent mutagenic activities in the Ames test with Salmonella typhimurium TA 98 after addition of rat liver metabolizing enzymes (S9 mix). The strain TA 100 showed no mutagenic response.

Animals↗

Genotoxicity study of CS (ortho-chlorobenzylidenemalononitrile) in Salmonella, Drosophila, and mice. Failure to detect mutagenic effects.

The lacrimatory agent CS was examined for genotoxic properties. In vitro, Salmonella typhimurium was exposed to CS at concentrations up to 1.5 mg per plate and reverse mutations were assayed. In vivo: male Drosophilae were fed with CS and sex-linked recessive lethal mutations in sperm cells were assayed using the Basc test. Further, mice were exposed to CS by oral or intraperitoneal administration; bone marrow erythrocytes were analysed for chromosomal mutations by means of the micronucleus test. All experiments failed to show a mutagenic activity of CS.

Animals↗

The mutagenic potential of hyperthermia and fever in mice.

The cytogenetic effects of hyperthermia resulting from climatic influences as well as from infections were studied. Whole-body exposure of NMRI mice to an elevated environmental temperature induced a high frequency of micronucleated polychromatic erythrocytes in bone marrow. Hyperthermia at high relative humidity was more effective in increasing body temperature and cytogenetic damage than at low RH. A sex-related difference in response to heat stress was observed. Hyperthermia on pregnant mice induced a significant increase in the incidence of micronucleated PEs in fetal blood cells. Parenteral administration of bacterial endotoxin, lipopolysaccharides, induced either hypothermia or hyperthermia. However, LPS-induced hypothermia as well as fever does not so far appear to produce cytogenetic damage.

Animals↗

Autoradiographic detection of 6-thioguanine-resistant lymphocytes of mice. A novel system in somatic mutagenesis testing.

After treatment of mice with ethylnitrosourea in vivo, induction of 6-thioguanine-resistant splenic lymphocytes was measured in vitro. The lymphocytes were mitogen-stimulated in presence of thioguanine. After a culture period of 30 h, TG resistance was determined by the ability of cells to incorporate [3H]thymidine. The results suggest that at this selection condition the majority of resistant cells stem from somatic mutations. Thus, the system is potentially useful as a screening assay for somatic mutagenesis testing. The problem of misleading results due to the presence of phenocopies was investigated by treatment in vitro with UV radiation or ethylnitrosourea.

Animals↗

Mutagenicity studies with the mouse spot test.

The mammalian spot test, which detects somatic gene mutations in mouse embryos, was investigated with selected chemicals to (a) further validate this test system (ENU, EMS, 2AAF, colchicine) and (b) evaluate the mutagenic potential, in a whole-mammal system, of environmental compounds that had been previously recognized as mutagens in other mammalian or submammalian test systems (1,2-dichloroethane, hydroquinone, nitrofurantoin, o-phenylenediamine, fried sausage extract). Of these substances, ENU, EMS and 2AAF were significantly mutagenic, 1,2-dichloroethane was probably weakly mutagenic. The ENU data were used to estimate the number of pigment precursor cells present at the time of treatment (day 9.25). We also describe in this report the use of a fluorescence microscope for classification of hairs from spots on the coat of C57BL/6JHan X T hybrids.

2-Acetylaminofluorene↗

Study of artificial flavouring substances for mutagenicity in the Salmonella/microsome, Basc and micronucleus tests.

Seventy-six compounds used as artificial flavouring substances in food products were studied for mutagenic properties by the use of the Salmonella/mammalian microsome test (Ames test), Basc test on Drosophila melanogaster and micronucleus test on mouse bone marrow. The following four compounds were mutagenic in Ames tests: ethyl nitrite, ethyl 3-phenylglycidate, 6-methylquinoline and musk ambrette. Of these, ethyl nitrite and musk ambrette also induced a significant (P less than or equal to 0.01) increase in sex-linked recessive lethal mutations in Drosophila. Two further compounds, ethyl 3-methyl-3-phenylglycidate and 4-n-propylanisole, appeared weakly mutagenic in Drosophila only. The result with 4-n-propylanisole was judged to be of equivocal biological significance. None of the flavouring substances induced micronuclei, i.e. cytogenetic damage in the bone marrow of mice.

Animals↗

5-Bromodeoxyuridine tablets with improved depot effect for analysis in vivo of sister-chromatid exchanges in bone-marrow and spermatogonial cells.

An improved 5-bromodeoxyuridine (BrdU) tablet technique for observation in vivo of SCE in mouse bone-marrow and spermatogonial cells is described. BrdU tablets were coated with agar as protecting barrier before subcutaneous implantation into mice. In comparison with the original tablets, the agar-coated tablets provided a slower and more uniform delivery of BrdU to the animals. This was corroborated (1) by recovering the undissolved portion of tablets at 1-2-h intervals, and (2) by quantitative determination of the BrdU levels in blood with the help of an analytical HPLC technique. The time required for complete dissolution of the coated tablets was considerably longer than that for the original tablets. This means that the dose of BrdU required for observation of SCE in mouse bone-marrow cells can be reduced accordingly. By using these modified tablets, therefore, undesired effects of high doses of BrdU on mutation (base-line SCE frequency) as well as on cellular replication and proliferation can be diminished. Moreover, the improved depot effect of the modified tablets facilitates the differential labeling of sister chromatids in mouse spermatogonia, a tissue containing cells with a relatively long DNA synthesis period.

Animals↗

Mutagenicity study of fried sausages in Salmonella, Drosophila and mammalian cells in vitro and in vivo.

The basic extract of pan-fried sausages was studied for mutagenic potential in seven test systems. Mutagenic activity was high in the standard Ames assay in the Salmonella typhimurium strains TA1538 and TA98 in presence of S9 mix. In vivo, in the intrasanguine host-mediated assay with strain TA98 on Aroclor-pretreated mice, the mutagenic activity of the extract was low. A borderline activity was seen in the SCE assay in vitro with V79 Chinese hamster cells in presence of S9 mix. No significant mutagenic action was found in the gene-mutation assay for thioguanine resistance with V79 cells, the Drosophila sex-linked recessive lethal test, the micronucleus test and the mammalian spot test.

Animals↗

How dangerous are falls in old people at home?

From a survey in six general practices information was obtained on 125 people aged 65 and over who fell in their own homes. Three fractured their femurs and 15 had other fractures; most of the rest suffered only trivial injuries. Twenty lay on the floor for more than one hour; none were known to have suffered hypothermia. One-quarter of these patients died within one year of the fall, five times as many as in an age- and sex-matched control group; while of those who lay on the floor for more than one hour, half died within six months of the fall. Factors associated with mortality from falls were impaired mobility, abnormal balance, and a disturbed pattern of gait. Falls at home in old age are often indicative of the presence of severe ill health.

Accidents, Home↗

Mutagenicity of cosmetics ingredients licensed by the European Communities.

As part of our investigation into mutagenic effects of environmental compounds, we studied chemicals allowed as ingredients of cosmetics according to the guidelines of the Council of the European Communities (27 July 1976). We used three systems, the Salmonella/microsome test, the Basc test on Drosophila and the micronucleus test on mouse bone marrow. Of the 31 chemicals tested, 15 were mutagenic in the Ames test; and of these, 5 were also mutagenic in the Basc test and 2 in the micronucleus test.

Animals↗

Description, classification and prevention of falls in old people at home.

One hundred and twenty-five people aged 65 and over who reported to their doctors that they had suffered falls at home were seen shortly after the fall by a research nurse who obtained a detailed history, based as far as possible on the patient's own statements and on an attempted reconstruction of the fall. Analysis of this description led to a classification of falls based on the nature of the displacing force. In turn, this classification can be used to highlight the necessary preventive action.

Accidents, Home↗

Prognosis of falls in old people at home.

One hundred and twenty-five people aged 65 and over in the Birmingham area who fell at home were followed up for one year after the fall had been reported by the general practitioner. They were compared with 125 control subjects matched for age and sex and drawn from the same doctors' lists. Two months after the fall, one control and 11 fallers had died. One year after the fall, eight controls and 32 fallers had died. The main factor associated with increased mortality was impaired mobility before the index fall.

Accidents, Home↗