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S Venitt

Publications and source records attributed to S Venitt.

At least 73 records · Page 4Linked to original sources
PubMed1984

Monitoring exposure of nursing and pharmacy personnel to cytotoxic drugs: urinary mutation assays and urinary platinum as markers of absorption.

In a study to determine whether hospital staff who handle cytotoxic drugs show signs of drug absorption, urinary mutagenicity assays gave positive results in a high proportion of non-exposed control subjects as well as in "exposed" hospital staff and were therefore considered unsuitable for routine monitoring. Determination of urinary platinum levels with atomic-absorption spectrophotometry of untreated urine may be a useful alternative. With this method platinum levels were below the reliable limits of detection in nurses and pharmacists who handled cytotoxic drugs (including platinum-containing drugs) and in controls. The urine of cisplatin-treated patients contained an average platinum level of 7 micrograms/ml, suggesting that contact with urine from patients undergoing intensive chemotherapy may be hazardous.

Absorption↗
PubMed1984

The hair-dye reagent 2-(2',4'-diaminophenoxy)ethanol is mutagenic to Salmonella typhimurium.

A new hair-dye ingredient, 2-(2',4'-diaminophenoxy)ethanol (2,4-DAPE), was described as being devoid of any genotoxic activity on the basis of a multi-laboratory study. Since 2,4-DAPE is a close analogue of 2,4-diaminoanisole (2,4-DAA), which is mutagenic and carcinogenic, we tested this claim by assaying 2,4-DAPE for bacterial mutagenicity. Two samples of 2,4-DAPE X 2HCl were synthesized by reduction of the corresponding dinitrophenoxyethanol and identity and purity were established by elemental analysis, NMR spectrometry, mass-spectrometry, UV-spectrophotometry, TLC and HPLC. Fresh aqueous solutions of 2,4-DAPE X 2HCl were assayed in several separate plate tests using S. typhimurium TA1538, TA97, TA98 and TA100, and E. coli WP2uvrA (pKM101), 3 plates per dose and 0%, 4%, 10% and 30% Aroclor 1254-induced rat-liver S9 in S9 mixes. We obtained negative results in TA100 and E. coli. Reproducible, statistically significant dose-related increases in revertants (up to 14 times the background) were obtained in frame-shift mutants of S. typhimurium in the dose range 10-80 micrograms per plate. Mutagenicity was S9-dependent, significant increases in revertants being obtained only with 50 microliter per plate or more of S9. 2,4-DAPE induced significant mutagenic effects at doses of less than 1 micrograms per ml in TA1538 and TA98 in fluctuation tests using 2% S9 in the S9 mix. In plate tests, 2,4-DAPE was less mutagenic (by a factor of about 8) than 2,4-DAA, which gave the highest mutant yields with 20 microliter S9 per plate (4% S9 in the S9 mix). 2,4-DAPE obtained commercially was about 8 times more mutagenic than our sample of 2,4-DAPE. After purification, the commercial product, now chromatographically identical with our own sample, gave plate-test results close to those obtained for our samples of 2,4-DAPE. A review of the published reports (in which 2,4-DAPE was claimed to be inactive in a variety of short-term tests) revealed: (a) the use of protocols for bacterial mutagenicity testing which, in the light of our own results, were probably too limited in scope, especially in the choice of conditions for metabolic activation; (b) insufficient information on the identification and purity of the samples of 2,4-DAPE tested in the published collaborative study.

Animals↗
PubMed1983

The development of anaerobic methods for bacterial mutation assays: aerobic and anaerobic fluctuation tests of human faecal extracts and reference mutagens.

Methods for performing microtitre fluctuation tests in an anaerobic enclosure have been devised in order to study the mutagenic activity of human faecal extracts under conditions of strict anaerobiosis. Under these conditions (monitored by growth of obligate anaerobes), two mutagens (4-chloromethylbiphenyl (4CMB) and potassium dichromate) were reproducibly mutagenic to Salmonella typhimurium TA 100 and Escherichia coli WP2uvrA(pKM101), respectively. We investigated the mutagenicity of aqueous extracts of faeces, prepared aerobically and anaerobically, collected from a single donor. Bioassay of 5 faecal extracts showed that 4 contained substances which promoted auxotrophic growth of his- and tryp- bacteria, and were therefore unsuitable for mutagenicity assay. The remaining extract (half of which was prepared aerobically, the other anaerobically) was assayed for mutagenicity in S. typhimurium TA 100. Reproducible dose-response curves were obtained with the aerobic extract and with the anaerobic extract when both were assayed under aerobic conditions. Negative results were obtained when the anaerobic or aerobic extracts were assayed anaerobically, under conditions where concurrent assays of 4CMB were positive. We conclude that bacterial fluctuation tests using reversion from auxotrophy to prototrophy as the genetic marker can be seriously compromised by the presence of substances (including amino acids) in the test material which promote auxotrophic growth. Moreover, it is clear that the results and interpretation of mutagenicity tests of faecal extracts are very dependent on whether air is present or absent during both extraction and assay.

Aerobiosis↗
PubMed1982

Mutagens in human faeces. Are they relevant to cancer of the large bowel?

1. Mutagenic activity has been detected in faecal extracts, prepared by a number of methods, from donors living under widely differing geographical, cultural and dietary circumstances. Faecal extracts cause point mutations in bacteria and chromosomal damage in cultured mammalian cells. 2. The claims that nitroso compounds are present in human faeces have been retracted, and the chemical nature of faecal mutagens is still unknown. Indirect evidence suggests the presence of several classes of mutagen. 3. The use of different methods of mutation assay gives conflicting estimates of the proportion of people who excrete mutagenic faeces. There is wide variation in mutagenic activity between different stool samples from one person, and between different stool samples from different people. There is conflicting evidence for inhibition or enhancement of the mutagenicity of reference mutagens by faecal extracts. The effects of air oxidation on the mutagenicity of faecal extracts have not been investigated in detail. 4. It has been claimed that the proportion of people excreting mutagenic faeces is higher in groups representing populations at high risk of large-bowel cancer than in groups at low risk of large-bowel cancer. For the reasons given in paragraph 3, these claims must be regarded as premature. 5. The part played by faecal mutagens in the aetiology of large-bowel cancer has yet to be determined.

Colonic Neoplasms↗
PubMed1981

Sister-chromatid exchanges before and after hair dyeing.

Sister-chromatid exchanges (SCE( in the peripheral lymphocytes of 13 women and 1 man were scored immediately before, 6 h after and 7 days after the application of a hair dye by a professional hairdresser under normal conditions. All the hair dyes used in this study gave positive results when tested in the Salmonella/microsome test for mutagenic activity. 6 volunteers showed increases and 8 showed decreases in mean numbers of SCE per cell 6 h after dyeing: 2 of these increases and 3 of the decreases wee statistically significant. when the mean SCE per cell of the who group were compared there were no significant difference between the pre-dyeing sample and the 2 samples taken 6 h or 7 days after dyeing. It was concluded that single applications of proprietary hair dyes cause no consistent increase in the SCE levels in the peripheral lymphocytes of the people taking part in this study.

Adult↗
PubMed1981

Studies on the mechanism of action of LS 1727, a nitrosocarbamate of 19-nortestosterone.

LS 1727, a nitrosocarbamate of 19-nortestosterone, was active against lymphoid, antimetabolite-sensitive, cell lines in vitro especially L1210 and Ehrlich ascites tumour lines. It was less effective against alkylating agent-sensitive lines such as the Walker 256 carcinosarcoma. These results suggested a possible antimetabolite mode of action but LS 1727 had no effect on deoxy-or ribonucleotide pool sizes in L1210 cells. Studies on macromolecular synthesis showed an early inhibition of DNA synthesis whilst RNA and protein synthesis continued for 24-48 hours. This was reminiscent of a classic alkylating agent-like effect. In vivo studies with specific alkylating agent-sensitive, or antimetabolite-sensitive tumours showed no antitumour activity although significant inhibition of Ehrlich ascites tumour cell growth was observed at high doses. In vitro cytotoxicity studies showed LS 1727 to be inactivated in the presence of mouse, rat and dog liver supernatants. This would explain the poor antitumour effects in vivo compared with the in vitro observations. Because LS 1727 is a nitrosocarbamate its possible mutagenic activity was investigated. LS 1727 was highly mutagenic but this property was also lost in the presence of a rat liver microsomal fraction. Although an effective cytotoxic agent in vitro LS 1727 is only effective in vivo at toxic doses.

Alkylating Agents↗
PubMed1980

Mutagenicity of nitrosated alpha-amino acid derivatives N-acetyl-N'-nitrosotryptophan and its methyl ester in bacteria.

DL-N-acetyl-N'-nitrosotryptophan (I) and its methyl ester (II), readily formed under mild conditions by the reaction of nitrite with N-acetyltryptophan or its methyl ester, are model compounds for the study of the nitrosation of alpha-amino acid side chains, considered relevant to possible role of nitrosation of peptides and proteins in the aetiology of gastrointestinal cancer. Both compounds were assayed for mutagenicity in a series of Escherichia coli WP2 strains (trp- leads to trp+) and in several strains of Salmonella typhimurium (his- leads to his+), in the presence and absence of a post-mitochondrial supernatant (S9) from livers of rats treated with Aroclor 1254. Compound I was mutagenic to the following E. coli strains: WP2; WP2uvrA; WP2pKM101; WP2-98 and TA 100. Compound II was consistently less mutagenic than compound I to the E. coli strains, inactive in S. typhimurium TA 98 and TA 100, but more active than I in TA 1535. Neither compound was detectably mutagenic to E. coli WP2 lexA. Addition of S9 did not enhance the mutagenicity of either compound, and in some cases reduced the mutagenic to any of the E. coli strains tested, and nitrite alone (at pH 7.1) was very feebly mutagenic at doses where molar equivalents of compounds I were markedly active. The rate of decay of compound I in pH 5.9 was closely paralleled by decay of its mutagenicity. These data and the pattern of cytotoxicity and mutagenicity in several DNA-repair mutants of E. coli suggest that both compounds react with DNA to form excisable DNA-adducts which cause mutation by error-prone repair.

Escherichia coli↗
PubMed1976

Mutagenicity of the food colour brown FK and constituents in Salmonella typhimurium.

The food colour Brown FK (EEC Serial No. 124) is a mixture of p-sulphophenylazo derivatives of m-toluylenediamine and m-phenylenediamine and is used in the UK for colouring kippers. Brown FK and its constituents were assayed for mutagenicity in Salmonella typhimurium TA 1535, TA 1537 and TA 1538. Samples of Brown FK from three manufacturers were mutagenic in TA 1538 (framshift mutant) when activated by a rat-liver supernatant fraction. Mutagenicity was linearly dose-dependent in the range of 0--3 mg/plate with activities ranging from 22 to 50 times the spontaneous mutation frequency. One sample of Brown FK was mutagenic in the absence of metabolic activation producing a 16-fold increase in mutation at 4 mg/plate. Two major constituents of Brown FK, 2,4-diamino-5-(p-sulphophenylazo)-toluene (I) and 1,3-diamino-4-(p-sulphophenylazo)benzend (II), each present at about 18% in the complete colour, were mutagenic in TA 1538. Mutagenicity was linearly dose-related in the range 0--1 mumol/plate, with slopes of 0.35 mutants/nmol for compound I and 1.5 mutants/nmol for compound II. This activity was dependent on metabolic activation. Four other major constituents, (di- and tri-substituted diamines) were inactive, as was sulphanilic acid, the major excretion product of Brown FK. The mutagenicity of Brown FK could be largely accounted for by the combined effects of compounds I and II. Earlier studies showed that compounds I and II were responsible for the acute myotoxic effects seen when Brown FK was given per os to rats and pigs. Azoreductive fission of I and II to reactive triamines by gut microflora was thought to be the main metabolic pathway by which Brown FK produced its myotoxic effects, and it is proposed that the mutagenic effects of Brown FK are probably mediated by a similar mechanism.

Azo Compounds↗