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Biomedical subjects

D Paton

Publications and source records attributed to D Paton.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1982

Evaluation of two suggested methods of deactivating organic carcinogens by molecular modification.

Earlier observations that substitution of the aromatic nucleus of an arylamino/nitro carcinogen with either a sulphonic acid substituent or two methyl groups placed ortho to the nitrogen substituent renders the molecule non-carcinogenic have been extended via studies conducted in vitro. 4-Aminobiphenyl-4'-sulphonic acid has been synthesized and found to be non-mutagenic in the Salmonella mutation assay when tested under conditions where 4-aminobiphenyl was mutagenic. It is concluded that this sulphonic acid derivative may prove non-carcinogenic to rodents. In contrast to the non-carcinogenicity and non-mutagenicity reported for 3,3',5,5'-tetramethylbenzidine, 3,5-dimethyl-4-aminobiphenyl is approximately as mutagenic as 4-aminobiphenyl. It is therefore concluded that this material is potentially carcinogenic and that the loss of mutagenic activity observed for tetramethylbenzidine may be a structurally specific rather than a general phenomenon. In contrast, 3,5-dimethyl-4-nitrobiphenyl was much less mutagenic than 4-nitrobiphenyl. 9,9'-Bijulolidyl, a derivative of 3,3',5,5'-tetramethylbenzidine, was also found to be non-mutagenic. The general significance of these findings to the employment of structure-activity relationships in the design of non-mutagenic/non-carcinogenic molecules is discussed.

Aminobiphenyl Compounds↗
PubMed1981

4-Chloromethylbiphenyl (4CMB): a novel mutagen and potential carcinogen.

The bacterial mutagenicity and cell transforming properties of the monocyclic alkylating agent benzyl chloride have been compared with those of its biphenyl analogue, 4-chloromethylbiphenyl (4CMB), and it is apparent that the addition of the second benzene ring greatly enhances biological activity. The possible reasons for this enhancement are discussed in relation to similar effects observed when comparing the activities of aniline with its biphenyl analogue, 4-aminobiphenyl (4AB). The marked activity observed for 4CMB, a stable and crystalline solid, suggests that it could prove useful as a direct-acting positive control test chemical for use in short-term mutagenicity tests.

Aminobiphenyl Compounds↗