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T A Connors

Publications and source records attributed to T A Connors.

At least 19 recordsLinked to original sources
PubMed1992

Alkylating agents.

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Alkylating Agents↗
PubMed1991

Alkylating agents.

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Alkylating Agents↗
PubMed1990

Alkylating agents.

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Alkylating Agents↗
PubMed1989

Reduction of nitromin to nitrogen mustard: unscheduled DNA synthesis in aerobic or anaerobic rat hepatocytes, JB1, BL8 and Walker carcinoma cell lines.

A novel route for the microsomal generation of nitrogen mustard from its N-oxide nitromin is demonstrated. The mustard was trapped as an adduct with diethyldithiocarbamate and estimated by capillary GLC. The enzyme responsible for this reduction could utilize either NADPH or NADH. Reduction occurred preferentially under anaerobic conditions. Purified cytochrome P450 reductase could carry out this reaction. Similar activities were seen using microsomal fractions from rat liver or liver derived BL8, JB1 or Walker 256 carcinoma cells, when these were expressed on a per mg of protein basis. Unscheduled DNA synthesis (UDS) was used as an index of activation of nitromin in these cell systems. In all instances, greater induction of UDS occurred in cells incubated with nitromin under anaerobic conditions.

Aerobiosis↗
PubMed1989

Has chemotherapy anywhere to go?

The methods used in the past to detect anticancer agents should be replaced by new approaches, where the aim is specifically to find treatments for the common solid cancers. Programmes have now been introduced which allow the rapid preclinical development and clinical trial of new classes of chemical. Provided sensitive markers of tumour response can be developed, new types of anticancer agent with activity against solid cancer should be discovered.

Animals↗
PubMed1988

What is toxicology?

1. The ultimate objective of toxicology is the reduction of morbidity and mortality that occurs in man as a result of exposure to toxic substances. 2. The present emphasis on 'strategic' research could divert funding to answer specific but largely irrelevant questions to the detriment of 'basic' research. 3. True advances can only be made if 'basic' research is supported to the same extent as 'strategic' research and if the regulation of environmental chemicals is based on good evidence from clinicians, epidemiologists and scientists.

Humans↗
PubMed1987

Effects of substituted 2-nitroimidazoles and related compounds on unscheduled DNA synthesis in rat hepatocytes and in non-transformed (BL8) and transformed (JB1) rat liver epithelial derived cell lines.

1. Using unscheduled DNA synthesis as an index, the possible interaction of a number of substituted nitroimidazoles, e.g. misonidazole, with cellular DNA has been investigated. Transformed (JB1), non-transformed (BL8) rat liver epithelial derived cell lines and freshly prepared rat hepatocytes have been used. 2. Under anaerobic or aerobic conditions, relative to cells exposed to a nitroquinoline-N-oxide standard, misonidazole and related nitroimidazoles were very poor at stimulating unscheduled DNA synthesis in JB1 or BL8 cells or in hepatocytes, even at the highest concentrations tested (10 mM). Under anaerobic conditions, metabolic activation did occur as judged from the time-dependent depletion of cellular reduced glutathione in all three cell types. 3. It was concluded that in hypoxic cells an important mode of action of such nitroimidazoles as chemotherapeutic sensitisers may be by their interaction with cellular thiols rather from their interaction with DNA. 4. Functionalisation of the nitroimidazole ring with a side chain containing an aziridine function, e.g. RSU-1069 (1-(2-nitro-1-imidazolyl)-3-(1-aziridinyl)-2-propanol), results in the induction of unscheduled DNA synthesis in cells exposed under both aerobic and anaerobic conditions. On a molar basis, however, this induction was not so great as that caused by the simple monofunctional alkylating agent 1-aziridineethanol itself. Methyl-substitution of the aziridine ring in RSU-1069 reduced the extent of unscheduled DNA synthesis. 5. With all the compounds tested, unscheduled DNA synthesis was greater in JB1 cells than in BL8s or in hepatocytes.

Animals↗
PubMed1987

Preliminary investigations into the involvement of the intestinal microflora in CNS toxicity induced by 1,3-dinitrobenzene in male F-344 rats.

Administration of a single oral dose of 20 mg/kg of 1,3-dinitrobenzene caused ataxia in germ-free male F-344 rats but not in conventional rats. Repeated oral dosing of 20 mg/kg, 1,3-DNB was required to cause ataxia in conventional rats. Considerable differences were observed between the uptake, tissue distribution and excretion of DNB in germ-free and conventional rats.

Administration, Oral↗
PubMed1977

Preparation and antitumor activity of 1-aryl-3,3-dimethyltriazene derivatives.

Several 1-aryl-3,3-dimethyltriazene derivatives have been synthesized and tested for their antitumor activity against the TLX5 lymphoma in mice. These compounds are characterized by the presence of a carbonyl group bound to the benzene nucleus in the para position to the triazene funciton. Three p-sulfamoyl derivatives have also been included and proved to be inactive. Among the carbonyl derivatives compounds 1 and 20, which can be used as reference, cause ILS of about 50%, respectively, at four and three dose levels. Compound 16, the o-nitro-phenylhydrazone of the hydrazide 1, is active at all six dose levels studied. The adduct 19, obtained from the same hydrazide and p-nitrobenzaldehyde, is active at four dose levels, and the ILS values at two optimum doses are significantly greater than those caused by compound 1.

Animals↗