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Biomedical subjects

B W Fox

Publications and source records attributed to B W Fox.

14 recordsLinked to original sources
PubMed1978

The interaction of dianhydrogalactitol with DNA in cultured Yoshida sarcoma cells.

Using alkaline sucrose gradient sedimentation centrifugation it was found that treatment of Yoshida sarcoma cells in culture for 1 h with increasing concentrations of dianhydrogalactitol (DAG) enhanced the sedimentation rate of DNA in a dose-dependent manner. There was no difference between the amount of protein which co-sedimented with DNA released from treated and untreated cells. When DNA was extracted from the cells using a p-amino-salicylate-phenol mixture, the protein content of DNA seemed not to be affected by DAG. The possibility that DAG could form interstrand cross-linking in cellular DNA was suggested from renaturation studies. The appearance of a fast sedimenting DNA in the alkaline sucrose gradient and the evidence for a cross-linked DNA detected by renaturation technique, only appeared later than 6 h after treatment. A similar delayed effect on the depression in the rate of DNA synthesis was also observed. These data suggest that the inhibition of DNA synthesis may be related to the delayed formation of DNA interstrand cross-linked.

Animals↗
PubMed1977

Characteristics of dimer formation, excision and DNA strand growth in Yoshida sensitive and resistant cells after ultraviolet irradiation.

The sedimentation properties of the nascent DNA of Yoshida sarcoma cells, sensitive and resistant to methylene dimethane sulphonate and cross-resistant to U.V. light, have been studied after irradiation with U.V. light at 11 and 22J/m2. It has been shown that the DNA formed immediately after irradiation with 11J/m2 is some eight to nine times longer than the calculated inter--dimer distance in both cell-lines. Differences were, however, observed between the two cell-lines, in that the absence of excision of dimers in the sensitive cells was accompanied by the formation of a DNA component of low molecular weight, whereas excision in the resistant line was not so accompanied. There are some similarities between the Yoshida tumour line sensitive to methylene dimethane sulphonate and the U.V.-sensitive line of Xeroderma pigmentosum.

Animals↗
PubMed1977

Collateral sensitivity between methylene dimethane sulfonate and halogenated methotrexate derivatives in the Yoshida sarcoma in vivo and in vitro.

A Yoshida lymphosarcoma line (YMDR8) resistant to methylene dimethane sulfonate (MDMS) showed collateral sensitivity against three halogenated methotrexates: 3'-bromomethotrexate (NSC-98580), 3'-bromo-5'-chloromethotrexate (NSC-98579), and 3',5'-dichloromethotrexate (NSC-29630); however, it was cross-resistant to methotrexate itself. Two other independently derived MDMS-resistant cell lines, YMDR7 and YMDR9, also demonstrated collateral sensitivity against 3'-bromomethotrexate, but with the latter, the origin of the "induced" sensitivity probably was not due to interference with antigenic or oncogenic properties of the cell line. When these agents were used in vivo (in Wistar rats) and in vitro, subpopulation changes within the tumor lines could be observed. The possible importance of this parameter in the development of such sensitivity is discussed.

Animals↗
PubMed1976

The time course of DNA repair following methyl nitro-nitrosoguanidine (MNNG) treatment of P388F lymphoma cells in culture. I. Alkali dissociable DNA lesions and their restitution.

The pattern of formation and rejoining of P388F cell DNA single strand breaks revealed by alkaline sedimentation centrifugation studies following treatment with methyl nitro-nitrosoguanidine (MNNG) has been studied. Three periods of single strand break formation have been recognised, an initial period during the first 4 h where breaks are rapidly formed and rejoined, a second (medial) time range of 10-15 h following treatment and a final stage where the formation of breaks appears to be related to cell killing processes. The initial phase is considered to be due to the production and repair of X-ray like DNA lesions whereas those of the medial time range are more comparable to the enzymatic processes associated with the repair of ultraviolet light-induced damage.

Cell Line↗
PubMed1976

The time course of DNA repair following methyl nitro-nitrosoguanidine (MNNG) treatment of p388f lymphoma cells in culture. II. DNA repair synthesis and its correlation with strand breakage.

Repair synthesis has been followed in P388F cell DNA following treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) using 5-iodo-deoxyuridine (IUdR) and [3H] thymidine combination. A pattern of repair synthesis was obtained, similar in its timing to the initial and medial stages of single-strand break formation and rejoining within the first 24 h after treatment. A higher base insertion frequency in relation to single-strand breaks occurs during the medial stage of repair. However, a fundamental problem with the use of iododeoxyuridine and [3H] thymidine ([3H] TdR) as a suitable measure of repair synthesis was encountered and a potential source of error in such experiments was observed.

Cell Line↗
PubMed1976

The sensitivity of HeLa and Chinese hamster (ovary) cells to methylene dimethane sulphonate.

HeLa and Chinese hamster (ovary) cells were exposed in vitro to methylene dimethanesulphonate (MDMS) and their survival of colony-forming ability was assayed in monolayer culture. Asynchronous cultures were exposed to the drug for the whole culture period but cell survival was complicated by the toxicity of formaldehyde which is a final breakdown product of the drug. A short treatment schedule of 15 min within the hydrolytic half life of the agent was therefore employed and the response of synchronous cultures of HeLa cells was then assayed throughout the course of the cells cycle. Cells were most sensitive at the beginning of the DNA synthetic phase (early-S) and most resistant at the end (late-S).

Cell Division↗
PubMed1976

The effect of dibromodulcitol on resting and dividing lymphoid cells.

The effect of dibromodulcitol (DBD) on the incorporation of labelled precursors into DNA and RNA fractions of PHA-stimulated human lymphocytes and of P388F lymphoma cells at various stages of their growth was studied. Both cell systems showed sensitivity to the drug within the concentration rage of 1-10 mug/ml. When DBD was added before phytohaemagglutinin (PHA), h.han RNA. In contrast, by adding DBD after PHA, RNA labelling was much more inhibited than DNA. In the latter case, the decrease in DNA labelling occurred only 24 h after drug treatment whereas RNA labelling was decreased 1 h after treatment. Levels of DBD which normally produced 30% inhibition in plating efficiency of P388F lymphoma cells affected uridine-5-T incorporation to a different extent at different stages of growth of the culture. Enhanced RNA labelling occurred in early exponential stage while at later stages of growth, RNA synthesis was depressed.

Adult↗
PubMed1975

Effect of methyl methanesulphonate (MMS) and methylene dimethanesulphonate (MDMS) on the template activity of DNA isolated from MDMS-sensitive and -resistant Yoshida cells.

Both methylene dimethanesulphonate (MDMS) and methyl methanesulphonate (MMS) cause the template activity of Yoshida cell DNA to decrease in a dose-dependent manner. The MDMS-resistant subline of Yoshida tumour is less sensitive in terms of DNA template activity than the MDMS-sensitive subline towards both agents. Although the difference in sensitivity is not reflected in the survival data after each agent, it does suggest that the DNA from each cell line differs in its capacity to function as an efficient template.

Animals↗
PubMed1975

The effect of methylene dimethanesulphonate (MDMS) on the conformation of DNA and its dependence on base composition.

The interaction of the alkanesulphonate, methylene dimethanesulphonate (MDMS) with DNA has been studied. Thermal denaturation studies on mixtures of MDMS and DNA showed a dose-dependent decrease of the melting temperature midpoint (Tm) of the DNA. In addition, an irreversible decrease in ultraviolet absorption (hypochromism) preceded the hyperchromic shift, the magnitude of the former being linearly related to both the relative concentration of MDMS and the G-C content of the DNA used. Neither the reduction in melting temperature nor the initial UV absorption decrease occurred after dialysis of the reaction mixture. Equimolar proportions of the hydrolysis products of MDMS did not give the same effects as observed with the unhydrolysed agent. A similar hypochromism followed by strand separation occurs when DNA is allowed to stand with MDMS at room temperature, the time of subsequent strand separation being related to the treatment level of the drug. A weak association of MDMS with DNA is considered to be involved resulting in a local compression of the helical structure in the vicinity of the G-C pairs. It is suggested that this conformational change may act as a substrate for repair enzymes in vivo.

Animals↗