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Biomedical subjects

J Doniger

Publications and source records attributed to J Doniger.

66 records · Page 4Linked to original sources
PubMed1981

Expression of initiated and promoted stages of irradiation carcinogenesis in vitro.

Evidence obtained utilizing X-irradiation and ultraviolet light irradiation with 12-O-tetradecanol-phorbol-13-acetate (TPA) for the induction of transformation of Syrian hamster embryo cells (HEC) suggests that there is more than 1 type of initiation of carcinogenesis. Initiated HEC are phenotypically transformed in the presence of TPA (15--20-fold enhancement) but are not necessarily committed to be transformed because some colonies reverted to normal morphology when TPA was removed. Both initiated and promoted HEC are also sensitive to hamster lymphotoxin. The frequency of transformation was reduced by at least 70%. The ability to recognize discrete morphologically altered colonies after TPA addition in vitro indicates that promotion is not merely escape from growth control.

Animals↗
PubMed1981

Ultraviolet light action spectra for neoplastic transformation and lethality of Syrian hamster embryo cells correlate with spectrum for pyrimidine dimer formation in cellular DNA.

Action spectra were determined for neoplastic transformation, production of pyrimidine dimers, and lethality in Syrian hamster embryo cells. Of wavelengths between 240 and 313 nm, the most effective were 265 and 270. The relative sensitivities per quantum for transformation, pyrimidine dimer production, and lethality were essentially the same at each of the wavelengths tested. This action spectrum for transformation, which is relevant to carcinogenesis, is similar to spectra obtained previously by measuring other cellular responses in either microbial or mammalian systems. Because the action spectra for cytotoxicity and transformation are the same as the spectrum for dimer production, DNA is suggested as the target for all these processes.

Animals↗
PubMed1980

The early and late modes of DNA replication in ultraviolet irradiated Syrian hamster embryo cells.

The nature of DNA replication in UV irradiated Syrian hamster embryo cells (HEC) was investigated by measuring the size distribution of nascent daughter strand DNA. During the early mode nascent strands are made in smaller pieces than in nonirradiated cells. The late mode begins when nascent strands recover to normal size. This was observed in HEC 5 h post-UV. When the late mode is operational, nascent strands elongate to parental size in greater than 2 h, whereas less than 3 h are required during early mode function. Evidence from split dose experiments demonstrates that the recovery of the size of nascent strands is not due to enhanced gap filling. Furthermore, pyrimidine dimers are probably recognized differently by the replication complex during early and late mode DNA synthesis. The late mode of replication could account for the ability of HEC to survive UV irradiation even though they are inefficient in both excision and postreplication repair.

Animals↗
PubMed1980

Human fibroblast strain with normal survival but abnormal postreplication repair after ultraviolet light irradiation.

Postreplication repair has been studied in ultraviolet light (UV)-irradiated fibroblast strains derived from eight apparently normal control donors and seven xeroderma pigmentosum patients. One control donor strain had an intermediate defect in postreplication repair similar to that in excision-deficient xeroderma pigmentosum fibroblasts. However, unlike the xeroderma pigmentosum strains, this control donor strain had normal UV-induced unscheduled DNA synthesis and normal survival after irradiation with UV. This unique fibroblast strain should after irradiation with UV. This unique fibroblast strain should be useful in studies designed to elucidate the possible role of postreplication repair in UV-induced carcinogenesis and mutagenesis.

Adolescent↗
PubMed1980

Excision and postreplication DNA repair capacities, enhanced transformation, and survival of Syrian hamster embryo cells irradiated by ultraviolet light.

The frequency of ultraviolet light (UV)-induced neoplastic transformation of Syrian hamster embryo cells (HEC) is enhanced 3- to 10-fold when the cells are first treated with either X-irradiation or with methyl methanesulfonate. Maximum enhancement occurs when the interval between the two treatments is 48 hr. The relevance of UV-induced transformation to neoplasia is confirmed because the transformation to neoplasia is confirmed because the transformants produce tumors when injected into nude mice. Excision and postreplication DNA repair were studied to determine whether the enhanced transformations were associated with either of these repair mechanisms. Independent of X-ray or of methyl methanesulfonate pretreatment, approximately 25% of the pyrimidine dimers are excised within 24 hr in cells irradiated with UV with 3 J/sq m. During this period, more than 70% of the genome of cells irradiated with UV has been replicated. Postreplication repair is measured by the time required to chase pulse-labeled nascent DNA strands to parental-sided DNA. Regardless of pretreatment, 1 and 3 hr are required for pluse-labeled DNA in control and irradiated (10 J/sq m) cells, respectively, to reach parental size. Therefore, no correlation is found between a change in the rate of excision or postreplication repair and enhancement of transformation. Relative to control cloning efficiency, the survival of HEC contain more than 10(5) pyrimidine dimers/genome. The level of survival is similar to the survival of human skin fibroblasts which excise pyrimidine dimers four to five times as efficiently. Moreover, postreplication repair cannot account for the ability of these cells to survive because it is three times slower than in human fibroblasts. Therefore, other repair mechanisms must be responsible for HEC survival and transformation.

Animals↗
PubMed1976

Human correxonuclease. Purification and properties of a DNA repair exonuclease from placenta.

An exonuclease, which hydrolyzes single-stranded DNA, has been purified from human placenta. It initiates hydrolysis at both the 3' and 5' termini of such DNA with equal facility, yielding 5'-phosphorylated oligonucleotides averaging 4 nucleotides in length. These oligonucleotides are released from both termini at equal rates with the same size distribution. Although not detectably active against intact native DNA, this enzyme can initiate hydrolysis at single-stranded breaks, creating a gap 30 to 40 nucleotides long. If a pyrimidine dimer is adjacent to this break, the enzyme, by virtue of its action at internal phosphodiester bonds, can excise such dimers. We refer to this exonuclease as human correxonuclease because of its excision capability.

Alkaline Phosphatase↗