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Biomedical subjects

D Paton

Publications and source records attributed to D Paton.

At least 37 records · Page 2Linked to original sources
PubMed1990

Lung antioxidant enzymes, peroxidation, glutathione system and oxygen consumption in catalase inactivated young and old Rana perezi frogs.

In the lung of Rana perezi no differences as a function of age have been found for any of the five major antioxidant enzymes, reduced (GSH), oxidized (GSSG) or glutathione ratio (GSSG/GSH), oxygen consumption (VO2) and for in vivo or in vitro stimulated tissue peroxidation. This frog shows a moderate rate of oxygen consumption and a life span substantially longer than that of rats and mice. Chronic (2.5 months) catalase depletion in the lung did not affect survival or any additional antioxidant enzyme, GSH, GSSG or in vivo and in vitro lung peroxidation in any age group. Only the GSSG/GSH ratio and the VO2 were elevated in catalase depleted old but not young frogs. After comparison of these results with those obtained in other animal species by other authors we suggest the possibility that decreases in antioxidant capacity in old age be restricted to species with high basal metabolic rates. Nevertheless, scavenging of oxygen radicals can not be 100% effective in any species. Thus, aging can still be due to the continuous presence of small concentrations of O2 radicals in the tissues throughout the life span in animals with either high or low metabolic rates.

Aging↗
PubMed1990

1-Chloromethylpyrene: a reference skin sensitizer and genotoxin.

1-Chloromethylpyrene (1-CMP) has been evaluated as a model mutagen and toxin related to the ultimate electrophiles derived from benzo[a]pyrene and 1-nitropyrene. It was mutagenic to Salmonella (greater than 100 pg/plate) and exceptionally reactive to DNA when assessed by the 32P-postlabelling technique. 1-CMP was inactive in a mouse bone micronucleus assay when administered by gavage, probably due to hydrolysis, whose kinetics have been studied (t1/2 approximately 23 min at 37 degrees C). However, as expected, it was a potent skin toxin as determined by its activity as a mitogen to mouse skin and its contact allergenicity, as determined using the local lymph node proliferative assay. It is concluded that 1-CMP will probably be a potent human skin carcinogen and contact allergen.

Animals↗
PubMed1990

Clinical presentation and investigation of patients proceeding to isotope lung scanning for suspected pulmonary embolism.

The presenting features of 250 consecutive patients who underwent a ventilation/perfusion lung scan for suspected pulmonary embolus (PE) were analysed. Ninety-six patients had lung scans highly suggestive of PE, with one or more unmatched segmental perfusion defects (scan positive), 86 had low probability scans (scan negative) and 68 an indeterminate scan. Scan positive patients were more likely to have a PaO2 of less than 10.7 kPa, an elevated P(A-a)O2 and an abnormal chest X-ray compared with scan negative patients but these measurements were of poor specificity. Furthermore, scan-positive patients had a higher incidence of lung disease. Localized chest wall tenderness was more common in scan-positive patients, occurring in 9% of patients, but there were no other significant differences in individual symptoms, signs or electrocardiographic findings between scan-positive and scan-negative patients. The diagnosis of PE should not be made on clinical grounds alone and all patients suspected of having a PE should at least undergo isotope lung scanning.

Adolescent↗
PubMed1990

Safety of late acetylcysteine treatment in paracetamol poisoning.

Twenty patients who had taken overdoses of paracetamol were treated with acetylcysteine between 12 and 24 hours after the incident. Although 19 patients had plasma paracetamol concentrations greater than those associated with a 90% risk of moderate to severe liver damage, this complication occurred in only seven (35%) individuals. No patient developed hepatic encephalopathy or acute renal failure and all recovered without sequelae. We conclude that acetylcysteine administration up to 24 hours following paracetamol overdose is not dangerous and may prevent further liver damage.

Acetaminophen↗
PubMed1988

Weak and unexpected mutagenicity to Salmonella of the rat hepatocarcinogen methapyrilene.

The rat liver carcinogen methapyrilene is shown to be a selective mutagen to strain TA1535 of Salmonella typhimurium when tested in the absence of S9 mix and using the standard plate-incorporation assay protocol. The activity observed was weak but was reproducible for a range of samples on many occasions of test and was not due to impurities. These data contrast with six earlier reports of the inactivity of this chemical in the Salmonella mutation assay.

Aminopyridines↗
PubMed1986

Mutagenicity to Salmonella of four derivatives of the azo mutagen 5I: some implications for structure--activity databases and the evaluation of combinations of mutagens.

A structure--activity study is described in which four new derivatives of the potent bacterial mutagen 5-dimethylaminophenylazoindazole (5I) have been evaluated for mutagenicity to Salmonella. As expected, monodemethylation of the -NMe2 group of 5I increased its mutagenic potency while replacement of the -NMe2 with a cyclic amine reduced it. However, replacement of the aromatic indazole -NH group (of 5I) by an -NMe group (yielding NMe5I) dramatically attenuated mutagenic potency, a reduction which was both unexpected and not reversed in the monomethyl analogue (NMeMA5I). In competition experiments NMe5I had an inhibitory effect on the mutagenic potency of 5I itself and on that of the nonazo mutagen 2-acetylaminofluorene 2AAF. The results illustrate some of the problems associated with evaluating mixtures for mutagenicity and of assuming simple structure--activity relationships in the absence of relevant experimental data.

Azo Compounds↗
PubMed1984

Mutagenicity to Salmonella of the mono methylamino and N-cyanoethyl analogues of 4-dimethylaminoazobenzene (DAB) and 6-dimethylaminophenylazobenzthiazole (6BT).

Replacement of one of the methyl groups of the carcinogens 4-dimethylaminoazobenzene (DAB) and 6-dimethylaminophenylazobenzthiazole (6BT) with a cyanoethyl (-CH2CH2CN) substituent dramatically increases their mutagenic potency to Salmonella (strain TA98). The corresponding monomethylamino derivatives (-NHCH3) are more mutagenic than the parent dimethylamino [-N(CH3)2] compounds, but substantially less mutagenic than the cyanoethyl derivatives. All of these mutagenic activities are liver-S-9-dependent. The very similar dose response curves observed for the two cyanoethyl compounds argues for the formation of a common electrophilic intermediate from each.

Animals↗
PubMed1983

Cyclic amines as less mutagenic replacements for dimethyl amino (--NMe2) substituents on aromatic organic compounds: implications for carcinogenicity and toxicity.

Replacement of the dimethylamino (--NMe2) group of the rodent liver carcinogens 4-dimethylaminoazobenzene (DAB) and 6-dimethylaminophenylazobenzthiazole (6BT) with a pyrrolidinyl group leads to a marked attenuation of their mutagenicity to S. typhimurium in vitro. Replacement with the 6-membered piperidinyl group leads to a virtual loss of mutagenic activity. These results are discussed within the context of a possible, albeit limited correlation between carcinogenic potency to rodents and mutagenic potency to S. typhimurium. Based on these observations, it is suggested that replacement of the --NMe2 group of a toxic/carcinogenic/mutagenic aromatic chemical by a cyclic amine substituent may produce a less toxic (etc.) analogue with similar gross molecular properties. The significance of weak (less than 2-fold increase) mutagenic responses is discussed in relation to potential carcinogenicity.

Azo Compounds↗
PubMed1983

Synthesis of 1,6-diaminopyrene from 1,6-dinitropyrene and its S9 dependent mutagenicity to S. typhimurium.

1,6-Dinitropyrene elicits a potent mutagenic response in a range of microorganisms in the absence of auxiliary metabolism (S9 mix). This activity is considered to be dependent upon nitroreductase enzymes endogenous to the marker organism producing electrophilic species from one or both of the nitro groups. In order to evaluate this suggestion 1,6-diaminopyrene has been synthesised, characterized and found to elicit a mutagenic response in strain TA98 of Salmonella typhimurium, but only when evaluated in the presence of S9 mix. The active dose-range of the diamino compound was 10(4) times higher than that of the parent dinitro compound.

Dose-Response Relationship, Drug↗
PubMed1982

Comparisons between carcinogenic potency and mutagenic potency to Salmonella in a series of derivatives of 4-dimethylaminoazobenzene (DAB).

8 derivatives of the rodent liver carcinogen 4-dimethylaminoazobenzene (DAB), all of known carcinogenicity in rodents, have been evaluated in the 3 major variants of the Salmonella mutation assay; the standard plate test of Ames et al., the pre-incubation assay of Yahagi et al. and the fluctuation assay of Gatehouse. Although 4 of these chemicals were reported to be non-carcinogenic, and 4 to be of greater carcinogenic potency than DAB, each was mutagenic in a least 2 of the assays. Further, no quantitative correlation between carcinogenic and mutagenic potency was evident in any of the assay employed. The parent carcinogen DAB, 5-dimethylaminophenylazoindazole (a non-carcinogenic bacterial mutagen) and 6-dimethylaminophenylazobenzthiazole (a carcinogenic bacterial mutagen) were administered to rats via intraperitoneal injection, followed, 26 h later, by a sub-acute dose of [14C] dimethylnitrosamine. The histopathological condition of the livers of the treated animals was assessed together with a determination of the extent and nature of methylation by DMN of the DNA in the livers according to the method of O'Connor. Disturbances in both the pathological and DNA-related parameters were observed for the 2 carcinogens while control levels were seen for the non-carcinogen. Within this context the value of short-term assays conducted in vivo is discussed, especially their potential to identify potent mammalian carcinogens from among a collection of structurally related bacterial mutagens.

Animals↗
PubMed1982

Synthesis of N7-hydroxyethylguanine and O6-hydroxyethylguanine. Markers for the reaction of ethylene oxide (EO) with DNA.

O6-Hydroxyethylguanine has been synthesized by reaction of mono-sodium glycolate with 6-chloroguanine. The crystalline product has been characterized using a variety of analytical techniques and compared with a sample of the corresponding N7-hydroxyethyl derivative. These 2 chemicals may prove useful as standards when studying the reaction of ethylene oxide (EO) with DNA.

Chemical Phenomena↗