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Biomedical subjects

M Fox

Publications and source records attributed to M Fox.

At least 235 records · Page 13Linked to original sources
PubMed1980

Relative mutagenicity of antineoplastic drugs and other alkylating agents in V79 Chinese hamster cells, independence of cytotoxic and mutagenic responses.

The mutagenic and cytotoxic effects of 4 antineoplastic drugs, vinblastine, vincristine, adriamycin and nitrogen mustard and of several monofunctional alkylating agents have been assayed in V79 Chinese hamster cells. Vincristine, vinblastine and nitrogen mustard did not significantly increase the frequency of TGRHGPRT- mutants but were were all highly cytotoxic. Adriamycin and the monofunctional alkylating agents were all significantly mutagenic even at the lowest doses tested (approx. 70% survival level). Induced mutant frequency increased linearly with increasing dose whereas dose-response curves for cytotoxicity for these effective mutagens invariably showed a shoulder followed by an exponential decline. At equitoxic doses the relative mutagenic effectiveness was MNU > ENU > EMS > MNNG > MMS greater than or equal to DMS. MNU was approx. 20 times more effective than MMS and DMS. Measurement of the total amount of alkylation and the relative amounts of reaction with individual DNA bases at approx. equitoxic doses of MNU and DMS indicated a significantly higher O6/N7 ratio after MNU (0.15) than after DMS (0.005). However, approx. equal numbers of mutants/10(5) cells/microM O6-Meguanine were induced by these 2 agents. These results support previous conclusions, that mutagenic and cytotoxic responses are independent in V79 cells.

Alkanesulfonates↗
PubMed1980

Excess thymidine is not mutagenic in Chinese hamster V79 fibroblasts.

The ability of thymidine to enhance the frequency of HGPRT-, 6-thioguanine resistant V79 cell mutants has been investigated as a function of post treatment growth interval. We have also studied the relative sensitivities towards exogenous thymidine of wild type and mutant cell lines. Our data imply that increases in mutant frequency following exposure of V79 cells to thymidine can be explained on the basis of a greater sensitivity of wild type cells compared with HGPRT deficient cells.

Animals↗
PubMed1980

Relationship between x-ray exposure and malignant transformation in C3H 10T1/2 cells.

The appearance of transformed foci after x-irradiation of the C3H 10T1/2 line of murine cells requires extensive proliferation followed by prolonged incubation under conditions of confluence. When the progeny of irradiated cells are resuspended and plated to determine the number of potential transformed foci, the absolute yield is constant over a wide range of dilutions and is similar to that observed in cultures that have not been resuspended. In addition, for cells exposed to a given x-ray dose, the number of transformed foci per dish is independent of the number of irradiated cells. These observations suggest that few, if any, of the transformed clones occur as a direct consequence of the x-ray exposure and challenge the hypothesis that transformed foci are the clonal products of occasional cells that have experienced an x-ray-induced mutational change. Rather, it appears that at least two steps are involved. We suggest that exposure to x-rays result in a change, for example, the induction or expression of some cell function, in many or all of the cells and that this change is transmitted to the progeny of the surviving cells; a consequence of this change is an enhanced probability of the occurrence of a second step, transformation, when these cells are maintained under conditions of confluence.

Animals↗
PubMed1980

The incorporation of O4-methylthymidine into V79A cell DNA when present in the cell culture medium.

When Chinese hamster V79A cells are cultured in the presence of O4-methyl-[6-3H]-thymidine the incorporation of this modified nucleoside into newly synthesised DNA is observed. The radioactivity incorporated has been identified as O4-methylthymidine by digesting the DNA to 3'-monophosphates with spleen phosphodiesterase followed by treatment with alkaline phosphatase to give O4-methylthymidine as the major radioactive product. The radioactivity associated with the latter co-chromatographs with authentic O4-methylthymidine in several chromatographic systems. Once incorporated the modified nucleoside appears to be rapidly removed from the DNA with half-life of 2-3 h. There is no evidence of demethylation of the O4-methylthymidine to give thymidine, in either the culture medium or within the cells once incorporated into DNA. Although the levels of incorporation observed are low, (being only 125 O4-methylthymidine residues per 10(8) thymidine residues at a modified nucleoside concentration of 10(-5) M), they may still be relevant as similar levels are apparently produced in the DNA of the cultured cells on treatment with biologically significant doses of carcinogenic alkylating agents.

Animals↗
PubMed1980

Evidence for the involvement of lesions other than O6-alkylguanine in mammalian cell mutagenesis.

Marked differences between the mutagenic efficiency of N-methyl-N-nitrosourea (MNU), a potent carcinogen, methyl methane sulphonate (MMS) and dimethyl sulphate (DMS), both weak carcinogens, have been reported at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and ouabain loci in V79 cells. Differences in levels of O6-guanine methylation produced by these alkylating agents, has been interpreted as indicating that O6-methylguanine is the DNA lesion specifically responsible for their mutagenic and carcinogenic effects. Because of the heterogeneity of molecular events which can result in forward mutation this conclusion seems unjustified. The development and characterisation of a reverse assay from 6-thioguanine resistance and HAT medium sensitivity (TG(R) and HAT(S)), to 6-thioguanine sensitivity and HAT medium resistance (TG(S) and HAT(R)) HGPRT(-)-->HGPRT+ in V79 cells, has allowed us to test the above hypothesis in a more specific way. Ethyl methane sulphonate, a weak carcinogen and MNU, both of which produce significant levels of O atom alkylation, were similarly effective mutagens in the reverse direction. At equitoxic doses, DMS was 40-60 fold less efficient. There was however, no quantitative correlation between numbers of revertants induced and measured levels of O6-alkylguanine. From these and other observations it is concluded that O6-alkylguanine is not the only potentially mutagenic lesion in mammalian cells.

Adenine↗
PubMed1979

Failure of caffeine to influence induced mutation frequencies and the independence of cell killing and mutation induction in V79 Chinese hamster cells.

Using V79 Chinese hamster cells and a replating assay, no effect of caffeine post-treatment on spontaneous or UV- or EMS-induced mutation frequencies to 8-azaguanine resistance was demonstrable. However, considerable potentiation of cell killing was observed. Previous reports that caffeine enhances induced mutation frequencies are explained by an artefact in the situ method used; a similar artefact may also explain the cumulative in situ mutation dose-response curves. Furthermore, the relationship between mutation induction and dose has been shown to be qualitatively distinct from that between cell killing and dose. These differences suggest that cell killing and mutation induction are mediated via independent mechanisms and that pre-mutational lesions may be qualitatively distinct from pre-lethal lesions.

Animals↗
PubMed1979

Dominance of a repair function for X-ray-, U.V.- and alkylating agent-induced damage in hybrids between mouse lymphoma cells of different sensitivity.

Cell lines resistant to IUdR and 6-thioguanine were isolated from a radiosensitive mouse lymphoma line LS and its radioresistant derivative AII respectively. Their biological and biochemical characteristics, as measured by plating in HAT medium IUdR and TG and by (14C) hypoxanthine and (3H) thymidine uptake were measured and found to be consistent with those expected for drug resistant cell lines. Two hybrid cell lines were isolated from crosses between the LS IUdRr line and AII TGr line and their radiosensitivity measured relative to that of the parental lines. Radioresistance was found to be dominant in both the hybrid lines as was resistance to EMS and U.V. to which the parental lines also show differential sensitivity. The ability to recover from sublethal damage after X-irradiation was found to be temperature sensitive in radiosensitive cells, an inverse effect being seen when LS cells were irradiated at 20 degrees C and held at 20 degrees C between dose fractions. Hybrid cells showed a normal amount of recovery from sub-lethal damage when compared with that in AII cells but this occurred at t slightly slower rate at 20 degrees "c than at 37 degrees C. Recovery from sub-lethal damage in AII cells was unaffected by lowering the temperature. These findings suggest that the radiosensitive cells may be temperature sensitive, in some step or steps in the ligation process.

Alkylating Agents↗
PubMed1979

Path analysis of environmental and genetic influences on blood pressure.

Familial aggregation of a trait (determined by the intraclass correlation coefficient) may result from genetic influence or from environment common to a household. The authors used path analysis to separate aggregation into the proportion of population variability due to genetic influence (h2 = heritability) and the proportion due to environment common to a household (c2). They used data from full siblings and maternal half siblings, aged two to 18 years, from Bogalusa, Louisiana, a biracial community. The statistically significant aggregation they found could be explained by either h2 or c2 except for two cases: systolic measurement in the pooled (black and white) sample requires h2; diastolic measurement in the white sample requires c2. The authors present a simplified explanation of the techniques they used.

Adolescent↗
PubMed1979

Renal transplantation with multiple arteries.

Out of a total of 184 transplant operations there were 27 kidneys with 2 or more renal arteries. Five of these were in 23 related transplants. Ischaemic times were increased compared with those of kidneys with single arteries, but the incidence and duration of acute tubular necrosis and also the length of time spent in hospital were similar in both groups. Excessive bleeding and other complications were no more common than following single arterial anastomosis. Kidneys with multiple arteries can be used safely if careful interrupted suturing is performed, the kidneys are perfused before and kept cool during the procedure and polar arteries are not tied.

Humans↗