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Biomedical subjects

A Zunino

Publications and source records attributed to A Zunino.

At least 19 recordsLinked to original sources
PubMed2001

Hydrogen peroxide: effects on DNA, chromosomes, cell cycle and apoptosis induction in Fanconi's anemia cell lines.

Fanconi's anemia (FA) is an inherited autosomal recessive syndrome; cells from FA patients are very sensitive to crosslinking agents and to oxygen. Epstein-Barr virus (EBV)-transformed lymphoblasts belonging to different FA complementation groups and normal EBV-transformed lymphoblasts were studied for their response to treatment with the oxidizing agent hydrogen peroxide (H2O2). The analysis of 8-hydroxy-2'-deoxyguanosine (8-OHdG) content in the DNA of untreated cells showed an increased basal level of damage in cells from the complementation groups FA-C and FA-E. H2O2-induced 8-OHdG was higher in FA than in normal cell lines. The removal of 8-OHdG after H2O2 treatment was significantly reduced in the cells from complementation group E. However, all FA cell lines showed a normal ability in the resealing of DNA breaks, at least soon after treatment. All cell lines were also equally efficient in the removal of damaged pyrimidines. Compared with normal cells, FA cell lines showed an increase in the baseline level of micronuclei, but not in the number of micronuclei induced by H2O2. Micronuclei in FA cells originated prevalently from chromosomal fragmentation and, at a minor extent, from chromosome loss. After H2O2 treatment, FA cell lines accumulated in G(2) phase to a greater extent than normal lymphoblasts. However, reversion of mutation in FA-A and FA-C cells did not result in the correction of this phenotype. In cells evaluated for apoptosis no ladder formation was found in FA-C, FA-E and corrected FA-C cells. In conclusion, among the FA cell lines examined, only FA-E showed a defect in the repair of H2O2-induced damage. On the other hand, differences found in the cell cycle and apoptosis might be due to irreversible changes occurring in FA cell lines as a consequence of the primary defect.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Chromosomal aberrations evaluated by CGH, FISH and GTG-banding in a case of AIDS-related Burkitt's lymphoma.

BACKGROUND AND OBJECTIVE: We have previously reported on a complex chromosome rearrangement [der(17)] in a B-cell line, BRG A, established from an AIDS patient with Burkitt's lymphoma (BL). The aim of the present study was the definition of der(17) composition and the identification of complete or partial chromosome gains and losses in two cell clones (BRG A and BRG M) derived from this patient. DESIGN AND METHODS: We applied comparative genome hybridization (CGH) to detect the DNA misrepresentations in the genome of the two cell clones. Findings from CGH and banding analysis could then direct the choice of probes for chromosome painting experiments to elucidate der(17) composition. RESULTS: CGH analysis identified gains of chromosomes 1q, 7q, 12q, 13q, 15q, 17p, 20p,q and losses of chromosomes 3p and 5q in BRG A and gain of chromosome 1q and loss in chromosome 6q in BRG M. Some of the detected alterations had already been described in lymphomas, while others appeared to be new. The combination of these techniques allowed a precise definition of der(17), composed by translocated regions from chromosomes 12 and 15. INTERPRETATION AND CONCLUSIONS: We demonstrated CGH to be a powerful tool in the identification of recurrent chromosome aberrations in an AIDS-related BL and in ascertaining the origin of marker chromosomes. We were also able to identify a different pattern of aberrations and assess an independent sequence of events leading to the 1p gain in the two subclones.

Aneuploidy↗
PubMed1999

Extensive cutaneous necrosis associated with anticardiolipin antibodies.

Extensive cutaneous necrosis (ECN) associated with antiphospholipid antibodies is a rare presentation. We describe 2 patients with ECN and high titers of anticardiolipin antibodies. The mechanism by which these antibodies act has not been established and there is still controversy regarding treatment of these patients without established guidelines. In the few documented cases the use of pulse steroid therapy, anticoagulants, fibrinolytic agents, plasmapheresis, or a combination of them has shown some benefit. Early recognition and treatment of the antiphospholipid syndrome may limit the extent of thrombotic complications that can result in tissue necrosis.

Adolescent↗
PubMed1998

Enteropathic arthritis in association with collagenous colitis.

A 46-year-old man simultaneously developed chronic seronegative non destructive oligoarthritis and chronic watery diarrhoea. Biopsies from the colorectal mucosa showed a thickened subepithelial collagen layer consistent with collagenous colitis. Collagenous colitis should be added to the list of causes of enteropathic arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

UV-sensitive rodent mutant cell lines of complementation groups 6 and 8 differ phenotypically from their human counterparts.

Rodent UV-sensitive mutant cell lines of complementation groups 6 and 8 are the genetic counterparts of human Cockayne syndrome CS-B and CS-A, respectively. The original mutant in this group, UV61, was described as defective in cyclobutane pyrimidine dimer removal after high doses of UV. We have examined the responses of several cell lines from group 6 to low doses of UV irradiation, and find that these mutants have wild-type capacity for DNA repair as indicated by incision, cyclobutane pyrimidine dimer, and (6-4) photoproduct removal. ERCC6, the product of the gene defective in CS-B and group 6 mutants, is implicated in the regulation of repair of actively transcribed genes in Cockayne syndrome; however, this protein clearly is not required for the processing of low levels of damage in CHO cells, which occurs remarkably efficiently, 40-50% of dimers being removed in both wild-type and group 6 mutants in 5 hours following 0.1 Jm(-2) of UV. The group 8 mutant cell line US31, on the other hand, is very deficient in repair of UV damage, showing a more extreme phenotype than is seen in the corresponding human syndrome CS-A. In both complementation groups, expression of mutations in a gene involved in regulation of DNA repair takes very different forms in human and rodent cells.

Animals↗
PubMed1996

Study on aneuploidy and p53 mutations in astrocytomas.

To determine whether a correlation exists between aneuploidy and p53 status in astrocytic tumors we analyzed 48 astrocytomas with different grades of malignancy for the presence of p53 mutations and aneuploidy of chromosomes 10 and 17 (Ch10, Ch17), known to be particularly involved with this type of tumor. We used polymerase chain reaction (PCR)-based denaturing gradient gel electrophoresis (DGGE) analysis on exons 5-8 of the p53 gene, and fluorescence in situ hybridization (FISH) analysis on interphase nuclei using chromosome specific pericentromeric probes, respectively. Our results showed that Ch10/Ch17 aneuploidy is a common early event in astrocytomas (90% of low grade tumors are aneuploid). p53 mutations and Ch17 aneuploidy are early events, but their incidence is not dependent on tumor grade. Loss of Ch10 is the only alteration that significantly correlates with tumor progression. No significant correlation between the presence of Ch10/Ch17 aneuploidy and p53 mutations was found. However, the coexistence of p53 mutations and aneuploidy, was observed in a subset of cases. The presence of p53 mutations appeared to be a significant predictor of a poor prognosis. In conclusion, genomic instability may or may not be associated with p53 mutations in astrocytomas, thus suggesting that other cellular determinants can also be responsible for the aneuploidy observed.

Adult↗
PubMed1991

Chromosomal assignment of human O6-methylguanine-DNA-methyltransferase gene by hamster-human somatic cell hybrids.

Using an in vitro assay to measure O6-methylguanine-DNA-methyltransferase (MT) activity in cell extracts from a panel of human-hamster cell hybrids, we were able to locate the human MT gene on chromosome 10. Chinese hamster cells have little or no MT activity and the presence of human chromosome 10 was a necessary condition for MT activity in cell hybrids. In some cell hybrids carrying chromosome 10, however, MT activity was not higher than that of hamster cells. As an explanation for this result, genetic determinants repressing MT expression and/or activity might be present in other human chromosomes carried by MT-negative cell hybrids. Partial hyperploidy of the hamster karyotype, variable activity of the parental human cell lines and changes during subculturing of the cell hybrids might also account for the lack of enzymatic activity in chromosome 10 containing hybrids.

Animals↗
PubMed1985

Assay of phenacetin genotoxicity using in vitro and in vivo test systems.

Phenacetin was assayed in a battery of five short-term tests. (1) In a DNA-repair test using various Escherichia coli strains, the drug was not directly genotoxic nor did it induce nonreparable DNA damage in the presence of rat liver S9 fractions, while it was weakly active following activation with hamster liver S9. (2) In the Ames reversion test (strains TA97, TA98, TA100, and TA102 of Salmonella typhimurium, phenacetin reverted only TA100, and only in the presence of hamster liver S9. Mutagenicity was related to the concentration both of the drug and of the above metabolic system. There was no activation with hamster kidney S9, uninduced chicken liver S9, or with a variety of liver S9 preparations from rats treated with enzyme inducers (Aroclor 1254, phenobarbital, or 3-methylcholanthrene) and/or glutathione depletors (diethyl maleate or buthionine sulfoximine). Hamster liver S9 compared favorably to rat and even more to chicken liver S9 fractions also in activating various promutagens [3-amino-1-methyl-SH-pyrido (4,3-b)-indole, 2-aminofluorene, aflatoxin B1, benzo[a]pyrene, and benzo[a]pyrene-trans-7,8-diol] and in decreasing the mutagenicity of direct-acting compounds (4-nitroquinoline N-oxide and sodium dichromate). (3) Phenacetin was borderline positive in a forward mutation test (6-thioguanine resistance) in V79 cells, only in the presence of hamster liver S9, and gave negative results in the presence of rat liver S9 or without any metabolic system. (4) Following in vivo treatment, the alkaline elution assay did not reveal any DNA fragmentation in bone-marrow cells of ip-treated mice or in liver cells of rats treated by gavage. Apparent DNA damage was instead observed in the kidneys of rats receiving the drug by gavage or in the liver following ip administration. However, the effect was prevented (liver) or reduced (kidney) by preliminary perfusion of the organs, which discards (liver) or makes uncertain (kidney) the hypothesis of a true in vivo DNA damage. (5) Phenacetin ip induced in mouse bone-marrow cells a poor yet statistically significant increase in sister chromatid exchanges.

Animals↗
PubMed1983

Alkaline DNA fragmentation, DNA disentanglement evaluated viscosimetrically and sister chromatid exchanges, after treatment in vivo with nitrofurantoin.

Nitrofurantoin was not positive as a carcinogen in long term assays. In vitro it was positive in some short term tests and negative in others. We have examined Nitrofurantoin for its capability of inducing DNA damage in vivo. With the alkaline elution technique, Nitrofurantoin appeared clearly positive in all the tissues examined (liver, kidney, lung, spleen and bone marrow). In the liver we also observed some cross-linking effect. In bone marrow cells Nitrofurantoin was also clearly positive in terms of sister chromatid exchanges (SCEs) induction. DNA damage in vivo was also examined with a viscosimetric method, more sensitive than alkaline elution. With this method the results were essentially negative, suggesting that the two methods detect different types of damage. In view of its positivity in many organs and in two short term tests in vivo, the carcinogenic potential of Nitrofurantoin should be reconsidered.

Animals↗
PubMed1983

Lack of correlation between the capability of inducing sister-chromatid exchanges in vivo and carcinogenic potency, for 16 aromatic amines and azo derivatives.

16 aromatic amines and azo derivatives were studied. They were: benzidine; 2-acetylaminofluorene; 3'-methyl-p-dimethylaminoazobenzene; o-aminoazotoluene; p-dimethylaminoazobenzene; 2,4-diaminotoluene; 4,4'-oxydianiline; 2,4-diaminoanisole; 4,4'-methylenedianiline; 2-naphthylamine; auramine O; rhodamine B; ponceau MX; 1-naphthylamine; p-aminoazobenzene and aniline. Carcinogenic potency and potency in inducing sister-chromatid exchanges (SCEs) in vivo were compared. SCEs were absolutely not correlated with carcinogenic potency. A lack of correlation was also found with mutagenicity in the Ames test. On the contrary, a statistically significant correlation existed between DNA damage and SCEs.

Carcinogens↗
PubMed1983

Quantitative correlation between carcinogenicity and sister chromatid exchange induction in vivo for a group of 11 N-nitroso derivatives.

The quantitative correlation between induction of sister chromatid exchanges (SCEs) in vivo and carcinogenic potency was examined for 11 nitroso derivatives and was compared with the correlation of alkaline DNA fragmentation in liver DNA in vivo and with the Ames test. The correlation between DNA adducts and SCEs was also evaluated. DNA damage was slightly more predictive and the Ames test less predictive than SCE evaluation. The predictivity of these tests for this class of compounds was compared with the predictivity shown for different classes of chemical compounds.

Animals↗