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Biomedical subjects

H G Suarez

Publications and source records attributed to H G Suarez.

At least 19 recordsLinked to original sources
PubMed1991

gsp mutations in human thyroid tumours.

The presence of gsp mutations at codons 201 and 227 in the gene coding for the alpha subunit of the GTP-binding Gs protein which stimulates adenylyl cyclase (AC) has been investigated in 31 samples of differentiated thyroid tumours, which had been previously characterized with respect to their adenylyl cyclase activity (ACA) before and after stimulation by thyroid-stimulating hormone (TSH). Polymerase chain reaction (PCR) amplification of DNA extracted from these tumours, followed by high stringency oligonucleotide probing, enabled the detection of mutations in three samples originating from tumours with high constitutive ACA, which was not significantly further stimulated by TSH. Two mutations were at codon 227 and replaced Gln227 by His or Lys, and one was at codon 201, with the substitution of Arg201 by Ser. Because thyrocytes belong to the subset of differentiated cells which are programmed to proliferate in response to elevated cAMP levels, the gsp mutations observed in some differentiated thyroid carcinomas probably contributed to their tumorigenic phenotype.

Adenocarcinoma↗
PubMed1990

Presence of mutations in all three ras genes in human thyroid tumors.

Polymerase chain reaction (PCR) amplification followed by oligonucleotide probing was used to investigate the presence of ras genes mutations in human thyroid adenomas and carcinomas. The results confirm the frequent occurrence of mutations in all three ras genes in both adenomas and carcinomas, in agreement with the hypothesis that the ras mutations may constitute early steps in thyroid tumorigenesis. No evident correlation between the frequency of ras mutations, the identity of the mutated ras gene, the position affected in the ras gene or the type of mutation and the pathological features is apparent. However, definitive conclusion on this point is precluded because of the small number of tumors examined at the present time.

Adenoma↗
PubMed1989

Activated oncogenes in human skin tumors from a repair-deficient syndrome, xeroderma pigmentosum.

The recessive autosomal hereditary disease, xeroderma pigmentosum (XP), is characterized by a high incidence of tumors in sun-exposed skin. The defect in early steps of excision repair of XP cells leads to hypermutability towards UV-mimicking agents. DNA from eight XP tumors were screened for activated transforming genes using 3T3 transfection. In two skin tumors isolated from a XP child, an activated N-ras oncogene was detected. Synthetic oligonucleotide probes were used to characterize the mutation in the ras gene. Both tumors were found to be mutated in the 61st N-ras codon from gln to his. The mutation was accompanied by an increase in the level of N-ras specific mRNA and in one transformant, by the alteration of the p21 protein. In the same tumors, c-myc amplification and over transcription, and Ha-ras gene rearrangement and amplification were also detected. Analysis of other XP tumors with eleven different oncogene probes revealed an amplification of the Ha-ras gene in 6 out of 10 cases. The normal skin fibroblasts from XP patients show normal pattern levels of N-ras, c-myc and Ha-ras sequences. The hypothesis is proposed that the presence of several oncogene alterations in the same tumor could be due to the high amount of UV-induced DNA lesions found in the exposed skin cells, in the absence of efficient repair.

DNA↗
PubMed1986

Interferon-induced phenotypic changes in human tumor cells relative to the effects of interferon on c-ras oncogene expression.

Three human tumor cell lines derived from an osteosarcoma (OHA cells), a bladder carcinoma (EJ cells), and a gastric sarcoma (SHAC cells) were passaged serially in the presence of human interferon-alpha (IFN-alpha) for extended periods of time. The long-term IFN-alpha treatment induced a partial reversion of OHA tumor cell phenotype as exemplified by inhibition of cell proliferation, lack of cellular overlapping in confluent cultures and marked reduction in tumorigenicity. In contrast, under the same conditions, long-term IFN treatment did not reverse but even potentiated some of the phenotypic characteristics (including tumorigenicity) of EJ and SHAC cells. In the three tumor cell lines, the transforming ability, genomic level, or expression of activated oncogenes, c-Ki-ras, c-Ha-ras, and N-ras, respectively, were unaltered with long-term IFN-alpha treatment. Our data indicate that IFN-induced phenotypic changes are not necessarily associated with changes in oncogene expression.

Cell Differentiation↗
PubMed1982

Increased activity of polynucleotide ligase in 5-iodo-2'-deoxyuridine and mitomycin C-pretreated simian virus 40 (SV40)-infected monkey kidney cells.

The DNA ligase activity has been studied in 5-iodo-2'-deoxyuridine (IUdR), mitomycin C (MMC) and IUdR + MMC-treated SV40-infected or mock-infected CV1C11 monkey kidney cells. The results have shown that : 1. The level of enzyme activity is about two or three times higher in IUdR or MMC-treated non-infected cells; 2. SV40 infection doubles the level of ligase activity in the untreated cells; 3. There is an additional increase of ligase activity in IUdR or MMC-treated SV40-infected cells; 4. When infected or mock-infected cells are treated with IUdR + MMC, there is no modification of the results obtained with each drug alone; 5. Two peaks of different S values are detected in a partial purification of the drug(s) or viral induced enzyme(s). The increase in the ligase activity in drug-treated cells is independent of semi-conservative DNA synthesis. The drug(s) and viral-induced enzyme(s) is the consequence of a "de novo" synthesis of proteins, as shown by cycloheximide treatment.

Animals↗
PubMed1978

Expression of "early" and "late" viral functions in a somatic cell hybrid between a mouse cell and a spontaneous yielder SV 40-transformed Chinese hamster cell.

A somatic cell hybrid (Cl. 6d) was originated from the fusion of mouse 3T3-4E) and spontaneous yielder SV 40-transformed Chinese hamster (CHK/SVLP AG) cells. During the early stages of its history, the C1. 6d hybrid underwent a rapid chromosome loss, preferentially loosing hamster chromosomes. This was not a constant tendency of the hybrid cells. As the parental CHK)SVLP AG cells, the hybrid cells were always found 100 per cent SV40 T-antigen positive. While CHK/SVLP AG cells infectious SV 40 DNA, V-antigen and virus were regularly detected, in the hybrid cells only infectious DNA was occasionally detected. This was not due either to the loww of an essential Chinese hamster gene(s) or to the presence of an inhibiting mouse cell component(s); it was apparently the consequence of inability of the cells to properly activate the resident SV 40 genome(s). After superinfection with SV 40 DNA, the hybrid cells-though capable of synthesizing SV 40 V-antigen--were unable to ensure virus assembly. Experimental evidence was obtained suggesting that SV 40 maturation is dependent of a cellular function(s).

Animals↗
PubMed1978

Transformation of normal diploid cells by isolated metaphase chromosomes of virus-transformed or spontaneous tumor cells.

Normal diploid human cells with a limited life-span in culture, as well as primary or secondary cell cultures of mouse or rat embryos, can be transformed in vitro (i.e. grow in soft-agar or low-serum medium) after a single exposure to metaphase chromosomes from SV40-transformed human or rat cells, Ad5-transformed human cells and several spontaneous human or mouse tumor cells. Chromosomes from normal diploid cells do not show any such transforming activity. As judged from the number of colonies formed in selective medium, the efficiency of transformation is, with some exceptions, of the order of 10(-5)--10(-6) and is generally higher for homologous than for heterologous transfers. A fraction of the colonies demonstrate abortive transformation. Nevertheless, using chromosomes from all but one donor cell population, at least one transferent cell line expressing a stable transformed phenotype has been established. Our results demonstrate that transformation of normal diploid cells by a presumptive chromosome-mediated gene transfer can be obtained with a variety of donor and recipient cells.

Adenoviridae↗
PubMed1978

Induction of infectious virus DNA and virus particles by mitomycin C in SV40-transformed mouse cells.

A line of SV40-transformed mouse cells (SV/3T3-4E) was isolated and four clones were derived from this line. Spontaneous production of small amounts of infectious SV40 DNA was detected in the parental line and in three out of the four clones tested, although no synthesis of virions could be demonstrated. The yields of SV40 DNA were significantly enhanced following treatment of these cells with mitomycin C and infectious virus particles became detectable occasionally.

Cell Line↗
PubMed1977

Simian virus 40-Chinese hamster kidney cell interaction. III. Characteristics of chemical induction in a clone of virogenic transformed cells.

A number of chemical and physical agents were screened to determine their effectiveness in inducing simian virus (SV40) production in a virogenic clone of SV40-transformed Chinese hamster cells. Mitomycin C (MC) was the most effective inducing agent, and MC induction was further characterized. It was found that levels of infectious SV40 DNA were increased above control levels as early as 6 h after addition of MC to the culture medium and reached maximum levels by 48 h. Virus capsid (V) antigen and virions followed with a lag of about 24 h. V antigen production was sensitive to hydroxyurea, suggesting a dependence on virus DNA synthesis. The proportion of virus-producing cells (infectious centres) and the virus burst per cell were both stimulated by MC. Studies of 3H-thmidine incorporation demonstrated that the rate of SV40 DNA synthesis was maximal at 48 h post-induction, at which time cellular DNA synthesis was almost abolished. Caffeine, at doses not toxic to non-induced cells, strongly inhibited SV40production in both non-induced and induced cells, suggesting some role for DNA repair mechanisms.

Animals↗
PubMed1976

Simian virus 40-chinese hamster kidney cell interaction. II. The semipermissivity of the cell system.

Throughout in vitro passages, Chinese hamster kidney (CHK) cells progressively lost susceptibility to SV 40 virus infection while remaining continuously susceptible to viral DNA infection. Upon infection with SV 40 virus or viral DNA, the CHK cell line supported viral DNA and virus replication at a low level. SV 40 transformed CHK cell lines spontaneously produced small amounts of viral DNA and virions. The percentage of virus-producing cells was low. Various clones derived from each of these lines behaved as the parental cell population, leading to the conclusion that each CHK cell, whether transformed or not with SV 40, is potentially permissive for this virus.

Animals↗
PubMed1975

Simian virus 40-chinese hamster kidney cell interaction. I. Relationship of chromosome changes to transformation.

After approximately 20 in vitro passages, Chinese hamster kidney (CHK) cell cultures transformed upon exposure to different strains of SV 40 can show a diploid modal chromosome number of 22 with chromosome counts exclusively or essentially in the diploid range (20-25). In primary culture and at the 5th-7th subculture, tumors produced in nude mice by such cells can display a diploid modal value of 22 chromosomes. Numerical chromosome variations and karyotype abnormalities observed in CHK cells transformed upon infection with SV 40, are apparently indistinguishable from those that can be observed in uninfected CHK cells undergoing "spontaneous"-transformation. These results indicate that polyploidization is not a necessary step either in the process of transformation or in that of tumorigenic conversion with SV 40.

Animals↗