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A Zunino

Publications and source records attributed to A Zunino.

18 recordsLinked to original sources
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↗
PubMed1982

DNA damage in liver, kidney, bone marrow, and spleen of rats and mice treated with commercial and purified aniline as determined by alkaline elution assay and sister chromatid exchange induction.

Aniline of unknown purity has been reported to induce spleen hemangiosarcoma in rats. Aniline has been found to be negative in terms of mutagenicity in both bacteria and yeasts. We have found that both commercial (already rather pure) and repurified aniline are clearly positive to a similar extent in inducing DNA damage in vivo in liver and kidney of rats. Both the commercial and repurified product are also clearly positive in induction of sister chromatid exchanges in vivo in male Swiss mice bone marrow cells. Liver, kidney, and bone marrow DNA damage was absent in male Swiss mice.

Aniline Compounds↗
PubMed1981

Differences in sister chromatid exchange (SCE)-induction in vivo by cyclophosphamide in murine strains.

The susceptibility of sister chromatid exchange (SCE)-induction in bone marrow cells by cyclophosphamide (CPA) was tested in DBA/2, AKR, C57BL/6J, C3Hf and BALB/c mice in vivo. Mice were treated with one i.p. injection of 0.4, 2.0 and 10.0 mg/kg body weight of CPA or of saline. The base-line level of SCE was similar in all the strains with about 3 SCE/cell. Increasing concentrations of CPA caused an increased level of SCE. At any dose level, differences in the SCE frequency were observed among the five strains. The greatest difference was seen at the dose of 10 mg/kg, when the DBA/2 strain reached the frequency of 25.5 SCE/cell, whereas 19.3, 12.9, 11.4 and 10.1 SCE/cell were seen respectively in AKR, C57BL/6J, C3Hf and BALB/c mice.

Animals↗
PubMed1979

[Induction of sister chromatid exchange (SCE) and incorporation of BUdR in mouse cells treated with methotrexate].

MTX (approx. DI 50) induced an approx. 140% increase in SCE over controls. Increasing the BUdR concentration from 10(-5) to 10(-4) M an approx. 135% increase in SCE over controls was also obtained. The quenching of the H33258 dye fluorescence, measured microspectrofluorimetrically, suggested an increased in corporation of BUdR in MTX treated cells, roughly compatible with almost a doubling of the SCE control level in absence of MTX. Thus, at least a large fraction of the MTX induced SCE increase appeared to be dependent from an enhanced BUdR incorporation.

Animals↗