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Biomedical subjects

Z Z Su

Publications and source records attributed to Z Z Su.

45 records · Page 3Linked to original sources
PubMed1985

Mutagenesis at putative apurinic sites in alkylated single-stranded DNA of parvovirus H-1 propagated in human cells.

The treatment of parvovirus H-1, a single-stranded DNA virus, with ethylnitrosourea immediately prior to infection of human cells, resulted in both virus mutagenesis and lethality (immediate hits). The incubation of treated virus, prior to inoculation, under conditions promoting the release of alkylated bases, slightly reduced the mutagenicity of ethylnitrosourea but significantly increased its killing effect (delayed hits). In untreated cells, the appearance of one apurinic/apyrimidinic site in viral DNA correlated with the formation of approximately one delayed lethal hit per virus. Cells which had been sublethally UV irradiated prior to infection, were able to overcome about 20% of the delayed lethal hits inflicted to ethylnitrosourea-treated H-1. This UV-enhanced reactivation was accompanied by viral mutagenesis and was not observed for immediate lethal hits. Therefore, UV irradiation of human cells appears to trigger a conditioned recovery response which might alleviate a block to the replication of single-stranded DNA containing apurinic sites, allowing these noncoding lesions to direct mutagenesis. UV-irradiated cells also displayed a mutator phenotype towards untreated parvovirus H-1. In contrast, ethylnitrosourea failed to induce human cells to cause mutagenesis of undamaged viral DNA, although it enhanced their ability to reactivate damaged virus.

Alkylation↗
PubMed1984

Inhibition and recovery of the replication of depurinated parvovirus DNA in mouse fibroblasts.

Apurinic sites were introduced in the single-stranded DNA of parvovirus minute-virus-of-mice (MVM) and their effect on viral DNA synthesis was measured in mouse fibroblasts. Approximately one apurinic site per viral genome, is sufficient to block its replication in untreated cells. The exposure of host cells to a sublethal dose of UV-light 15 hours prior to virus infection, enhances their ability to support the replication of depurinated MVM. Cell preirradiation induces the apparent overcome of 10-15% of viral DNA replication blocks. These results indicate that apurinic sites prevent mammalian cells from replicating single-stranded DNA unless a recovery process is activated by cell UV-irradiation.

Animals↗
PubMed1982

Direct and indirect effects of ultraviolet light on the mutagenesis of parvovirus H-1 in human cells.

U.v. radiation is directly mutagenic for the single-stranded DNA parvovirus H-1 propagated in human cells. Mutation induction in the progeny of u.v.-irradiated virus increased linearly with the dose and could be ascribed neither to an increased number of rounds of viral replication nor to the indirect activation of an inducible cellular mutator activity by the u.v.-damaged virus. The level of mutagenesis among the descendants of both unirradiated and u.v.-damaged H-1 was enhanced if the host cells had been exposed to sublethal doses of u.v. light before infection. This indirect enhancement of viral mutagenesis in pre-irradiated cells was maximal at multiplicities lower than 0.2 infectious particles/cell. The frequency of mutations resulting from cell pre-irradiation was only slightly higher for u.v.-irradiated than for intact virus. Thus, the induced cellular mutator appeared to be mostly untargeted in the dose range given to the virus. U.v.-irradiation of the cells also enhanced the mutagenesis of u.v.-irradiated herpes simplex virus, a double-stranded DNA virus ( Lytle and Knott , 1982).

Cell Line↗
PubMed1981

Indirect induction of mutagenesis of intact parvovirus H-1 in mammalian cells treated with UV light or with UV-irradiated H-1 or simian virus 40.

The frequency of mutants among the descendants of intact parvovirus H-1 was increased when cells of human and rat origin were exposed to UV light prior to infection. An enhanced mutagenesis of intact H-1 could be induced to almost the same extent in unirradiated cells by preinfecting them with H-1 or simian virus 40 that had been irradiated with UV light. The expression of an enhanced mutagenesis of unirradiated H-1 after cell treatment with UV light or UV-irradiated virus was delayed, transient, and dose-dependent, and it was dependent on de novo protein synthesis.

Animals↗
PubMed1981

Mutagenesis of intact parvovirus H-1 is expressed co-ordinately with enhanced reactivation of ultraviolet irradiated virus in human and rat cells treated with 2-nitronaphthofurans.

The exposure of human or rat cells to non-toxic concentrations of two 2-nitronaphthofuran derivatives activated co-ordinately the transient expression of mutator and repair activities. These activities gave rise to both an increase in the mutagenesis (enhanced mutagenesis, EM) and survival (enhanced reactivation, ER) of unirradiated and u.v.-irradiated parvovirus H-1 used as respective probes. The kinetics of expression was the same for mutator and repair activities and for the two chemicals studied. The dose-responses of these activities were also parallel for a given chemical, but one of the furan derivatives exerted its inducing effect at concentrations 20-25 times lower than the other derivative. Both EM and ER were depressed by cycloheximide, and inhibitor of de novo protein synthesis. This is the first report which shows that chemicals can enhance the mutagenesis of undamaged DNA by activating the expression of mutator functions in mammalian, including human, cells. The ability of the two 2-nitronaphthofuran derivatives to trigger EM and ER was found to correlate with their reported mutagenicity in a conventional bacterial test system.

Animals↗
PubMedDate not supplied

Ultraviolet-irradiated simian virus 40 activates a mutator function in rat cells under conditions preventing viral DNA replication.

The UV-irradiated temperature-sensitive early SV40 mutant tsA209 is able to activate at the nonpermissive temperature the expression of mutator and recovery functions in rat cells. Unirradiated SV40 activates these functions only to a low extent. The expression of these mutator and recovery functions in SV40-infected cells was detected using the single-stranded DNA parvovirus H-1 as a probe. Because early SV40 mutants are defective in the initiation of viral DNA synthesis at the nonpermissive temperature, these results suggest that replication of UV-damaged DNA is not a prerequisite for the activation of mutator and recovery functions in mammalian cells. The expression of the mutator function is dose-dependent, i.e., the absolute number of UV-irradiated SV40 virions introduced per cell determines its level. Implications for the interpretation of mutation induction curves in the progeny of UV-irradiated SV40 in permissive host cells are discussed.

Animals↗
PubMedDate not supplied

Transfer of a dominant-acting tumor-inducing oncogene from human prostatic carcinoma cells to cloned rat embryo fibroblast cells by DNA-transfection.

The mechanism by which normal human prostate cells develop into prostatic carcinoma cells is not presently known. In the present study we have tested the hypothesis that specific prostatic carcinomas develop as a consequence of activation of a cellular gene(s) with transforming and tumorigenic potential. To test this possibility, high molecular weight DNA was extracted from the human prostatic carcinoma cell line, LNCaP, and cotransfected with a dominant acting neomycin resistance gene, pSV2-neo, into a subclone of Fischer rat embryo fibroblast (CREF) cells, CREF-Trans 6, and NIH-3T3 cells. Cells were selected for growth in G418 and pooled resistant colonies, which were morphologically normal, were injected subcutaneously into athymic nude mice. Tumors developed in several of the animals inoculated with LNCaP DNA-transfected CREF-Trans 6 cells and they were established in monolayer culture. In contrast, no tumors developed in nude mice injected with untransfected CREF-Trans 6 cells, pSV2-neo transfected CREF-Trans 6 cells or LNCaP plus pSV2-neo DNA-transfected NIH-3T3 cells. DNA from the first cycle tumor-derived CREF-Trans 6 cell lines, which were morphologically transformed in monolayer culture, was cotransfected with pSV2-neo a second time into CREF-Trans 6 cells and transfected cells, which were still morphologically normal, were injected into nude mice. Tumors developed in animals and they were again established in tissue culture. Secondary transfectants isolated from animals were morphologically transformed and grew with high efficiency in agar. Both primary and secondary LNCaP-transfected-nude mouse tumor derived-CREF-Trans 6 cells contained human repetitive (Alu) sequences. Although the pattern of Alu integration in the tumor derived CREF-Trans 6 cells were different for different tumors, both primary and secondary tumors contained a single apparently common-sized Alu fragment. The present study indicates that the human prostatic carcinoma cell line, LNCaP, contains a dominant-acting tumor-inducing oncogene which does not induce morphological transformation of CREF-Trans 6 or NIH-3T3 cells in monolayer culture. In addition, the CREF-Trans 6 cell line can detect this tumor-inducing gene function, whereas this activity is not observed in DNA-transfected NIH-3T3 cells.

3T3 Cells↗
PubMedDate not supplied

Apoptosis mediates the selective toxicity of caffeic acid phenethyl ester (CAPE) toward oncogene-transformed rat embryo fibroblast cells.

The active component of the folk medicine propolis, caffeic acid phenethyl ester (CAPE), displays selective toxicity toward cloned rat embryo fibroblast (CREF) cells transformed by a spectrum of diverse acting oncogenes. Identification of the mode of action of CAPE should provide useful information for possible applications of this compound for cancer therapy. The present study uses a series of oncogene transformed, oncogene-reverted and CAPE-resistant oncogene transformed CREF cells to investigate the mechanism underlying the increased sensitivity of transformed cells to CAPE. A direct relationship exists between the cytotoxic effects of CAPE and the induction of DNA fragmentation and apoptosis. DNA degradation into nucleosomal fragments and apoptotic shifts in DNA cell cycle profiles occur in CAPE-treated CREF cells transformed by wild-type 5 adenovirus (Ad5), a mutant Ad5 (H5hr1), the wild-type Ad5 E1A transforming gene, v-src, Ha-ras and the human papilloma virus type 18 transforming genes (HPV-18). In contrast, untransformed CREF cells, human fibroblast expression library-induced morphological revertants of Ad5- and v-src-transformed CREF cells, and Krev-1 expressing revertant Ha-ras-transformed CREF cells are resistant to CAPE-induced toxicity and apoptosis. Similarly, mutant Ad5-transformed CREF cells selected by step-wise growth in increasing concentrations of CAPE are resistant to growth inhibition and apoptosis induced by CAPE. These findings indicate that expression of the transformed phenotype by rodent cells evokes sensitivity to CAPE induced toxicity through apoptosis. The acquisition of CAPE sensitivity in rodent cells is independent of the mode of action of the oncogenic agent. CAPE may prove useful as an antiproliferative agent in cancer cells transformed by mechanistically diverse acting oncogenes.

Animals↗