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P Menichini

Publications and source records attributed to P Menichini.

26 records · Page 2Linked to original sources
PubMed1990

Extent of helix perturbation associated with DNA modification by the o-acetyl derivative of the carcinogen 4-hydroxyaminoquinoline-1-oxide.

Duplex unwinding associated with DNA modification by 4-acetoxyaminoquinoline-1-oxide, a model ultimate carcinogen of 4-nitroquinoline-1-oxide, has been determined by the agarose gel electrophoresis band-shift method. An average unwinding angle per stable adduct of -15.1 degrees +/- 1.5 degrees for negatively supercoiled topoisomers and -6.5 degrees +/- 1.4 degrees for positively supercoiled topoisomers was obtained. Because of the different proportion of stable adducts (dGuo-N2-AQO, dGuo-C8-AQO, dAdo-N6-AQO) between negatively (8:1.5:0.5) and positively (5:2.5:1) supercoiled topoisomers, the difference in unwinding angles is suggestive of a diverse contribution of the various adducts to the overall conformational change. Since the largest unwinding angle was coupled with the highest proportion of dGuo-N2-AQO adduct, it is likely that this adduct is the most distortive lesion. A contribution of sites of base loss to DNA unwinding was also observed.

Aminoquinolines↗
PubMed1989

The presence of amplified regions affects the stability of chromosomes in drug-resistant Chinese hamster cells.

The stability of chromosomes carrying amplified CAD (carbamyl phosphate synthetase-aspartate transcarbamylase-dihydroorotase) or DHFR (dihydrofolate reductase) genes was studied in V79 Chinese hamster cell derivatives resistant to PALA (N-phosphonacetyl-L-aspartate) and MTX (methotrexate), respectively. Cells were maintained in the presence of the selective drugs during the study. In both metaphase chromosomes and interphase nuclei, amplified regions were localized by in situ hybridization. In MTX-resistant cells, the amplification-bearing chromosome moved sluggishly at anaphase and gave rise to bud-shaped formations in interphase nuclei. It is suggested that these buds could eventually separate as micronuclei. In both MTX- and PALA-resistant cells, amplified DNA was observed in micronuclei in interphase and in displaced chromosomes in metaphase. Finally, amplification-bearing dicentric chromosomes were found in both drug-resistant cell lines. Cumulatively, these observations indicate that the presence of the amplified region in a chromosome renders it unstable: chromosomes bearing an amplified region tended to be excluded from cells, and rearrangements were more frequent than in normal chromosomes.

Animals↗
PubMed1989

In vitro DNA modification by the ultimate carcinogen of 4-nitroquinoline-1-oxide: influence of superhelicity.

The effect of DNA tertiary structure on in vitro modification by 4-acetoxy-aminoquinoline-1-oxide (Ac-4-HAQO) was investigated. The reactivity of pAT153 plasmid DNA depended on the conformational state of the molecule: it progressively decreased according to the decrease of the superhelical tension, being negatively supercoiled DNA about two times more susceptible than singly-nicked relaxed DNA. HPLC of the three main Ac-4-HAQO adducts showed that 3-(deoxyguanosin-N2-yl)-4-aminoquinoline-1-oxide, N-(deoxyguanosin-C8-yl)-4-aminoquinoline-1-oxide and 3-(deoxyadenosin-N6-yl)-4-aminoquinoline-1-oxide accounted for 50, 25 and 10% of total quinoline DNA base adducts in all DNA conformations tested, except in the negatively supercoiled topoisomers where they accounted for 80, 15 and 5% respectively. DNA modification by Ac-4-HAQO resulted also in the formation of apurinic/apyrimidinic sites and in strand scissions. The quantification of these damages revealed that they represent an important fraction of all damaging events and that their yield is also influenced by DNA superstructure. Thus, these lesions must be considered as important DNA damage induced by Ac-4-HAQO.

4-Nitroquinoline-1-oxide↗
PubMed1989

Perturbation of DNA tertiary structure by physical and chemical carcinogens: effects on DNA repair processes.

DNA within the cell is organized into higher-order structures characterized by negative supercoiling. Supercoiling is a property of any DNA molecule lacking ends capable of rotation. Parameters defining the properties of supercoiled DNA are significant for the description of the reactive state of DNA molecules. We have investigated whether physical and chemical DNA modifying agents alter the parameters describing the DNA tertiary structure. The variations in DNA tertiary structure of partially relaxed topoisomers obtained from plasmid DNA have been studied by one dimensional agarose gel electrophoresis, a technique allowing the measurement of alterations in the degree of supercoiling equivalent to fractions of superhelical turns. Unwinding angles of 8.5 degrees for pyrimidine dimers and of 8.5 degrees for acetyl-4-hydroxyaminoquinoline-I-oxide (Ac-4-HAQO) adducts have been determined by titrating for each topoisomers the number of damaged sites necessary to reduce the superhelical turns by one. Analogous unwinding was observed for topoisomers obtained from in vivo irradiated plasmid DNA. We have also shown that local alterations in DNA structure caused by UV irradiation inhibit bacterial type I DNA topoisomerases. In addition, we have demonstrated that E. coli mutants lacking DNA topoisomerase I are sensitive to UV light. The pronounced inhibition of DNA synthesis as well as the chromosome instability observed after UV irradiation of this strain, suggest that DNA topoisomerase I might be involved in those cellular responses elicited by the proximity of damaged bases to sites of active replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinogens↗
PubMedDate not supplied

Study of 4-NQO induced mutations at the HPRT locus in CHO cell lines. Possible influences of preferential DNA-repair on the mutational spectrum.

In the attempt to determine the possible influence of excision repair processes on 4-NQO mutational spectra in mammalian cells, 4-NQO-induced mutants at the hprt locus were isolated in excision repair proficient (AA8) and deficient (UV5) CHO cell lines. DNA sequencing data on these mutants revealed that DNA repair may indeed modulate the induced mutational spectrum. In particular, more splice mutations were found in the repair proficient than in the repair deficient cells. This can be interpreted by a difference in repairability of the two principal 4-NQO G-adducts or by the existence of a transcription-coupled DNA preferential repair process.

4-Nitroquinoline-1-oxide↗