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Biomedical subjects

W SZYBALSKI

Publications and source records attributed to W SZYBALSKI.

At least 19 recordsLinked to original sources

MITOMYCINS AND PORFIROMYCIN: CHEMICAL MECHANISM OF ACTIVATION AND CROSS-LINKING OF DNA.

Mitomycins and porfiromycin, generally nonreactive in the natural oxidized state, behave as bifunctional "alkylating" agents upon chemical or enzymatic reduction, followed by spontaneous loss of the tertiary methoxy (hydroxyl) group and formation of an aromatic indole system. Thus activated, mitomycins and porfiromycin react in vitro with purified DNA, linking its complementary strands. A high content of guanine and cytosine favors this cross-linking reaction, which is the basis of the lethal effect in vivo of these antibiotics. The activation and cross-linking reactions are discussed in terms of reactive sites on the mitomycin and DNA molecules.

Anti-Bacterial Agents↗

Genetics of human cell lines. III. Incorporation of 5-bromo- and 5-iododeoxyuridine into the deoxyribonucleic acid of human cells and its effect on radiation sensitivity.

The human cell line D98S can be cultivated indefinitely in the presence of up to 3 x 10(-5)M 5-bromodeoxyuridine (BUDR), without loss of cell viability. During this time, BUDR is incorporated into both strands of the DNA molecules, replacing up to 45 per cent of the thymidine and thereby rendering the cells highly sensitive to UV light and to x-rays. Cells grown for a limited period of time in the presence of 5-iododeoxyuridine (IUDR) become UV-sensitized, while prolonged cultivation with IUDR results in the loss of cell viability. The properties of the BUDR label permitted the demonstration that: (a) human DNA replicates in a "semiconservative" manner; (b) the degree of radiosensitization of BUDR-treated cells depends on whether the DNA has been substituted in one strand only ("unifilarly") or in both strands ("bifilarly"); (c) functional human DNA is produced during partial inhibition of protein synthesis. The potential applicability of this new rational principle of radiosensitization to the radiotherapy of neoplastic diseases is discussed.

Antimetabolites↗