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Biomedical subjects

F Baccichetti

Publications and source records attributed to F Baccichetti.

At least 91 records · Page 5Linked to original sources
PubMed1976

DNA repair and recovery in Escherichia coli after psoralen and angelicin photosensitization.

The correlation between DNA repair and recovery of biological functions was studied using three wild type strains of Escherichia coli and two skinphotosensitizing furocoumarins, psoralen and angelicin, which are well known specific reagents of the pyrimidine bases of DNA. In addition to mono-adducts psoralen is able to form a high number of inter-strand cross-links, while angelicin forms only mono-adducts. Both of these damages were repaired, in a short time, in the following way: at first DNA was cut into small pieces that were then rejoined into molecules of normal size, free from cross-links, while the furocoumarin residue was split from DNA almost quantitatively. Recovery of biological functions was studied performing photosensitization experiments in such a manner that the same amounts of psoralen or of angelicin were linked to bacterial DNA. DNA synthesis, tested just after the damage, was inhibited in a similar extent by both drugs. The same bacteria, however, showed a very different colony-forming capacity; angelicin was much less effective than psoralen with a D37 dose about 2.7 times higher. A similar picture was obtained studying DNA synthesis at different times after photosensitization: in the bacteria damaged by angelicin it was restored while no recovery was observed in cells photosensitized by psoralen. These results suggest that both mono-adducts and cross-links can be chemically repaired more or less in a quantitative measure, but that repair of cross-links in much less effective on cell recovery; this behaviour is very probably connected with the different repair mechanisms of mono-adducts and of cross-links.

Coumarins↗
PubMedDate not supplied

Photobiological properties of 1-(3'-hydroxypropyl)-4,6,8-trimethylfur.

A new furoquinolinone derivative, 1-(3'-hydroxypropyl)-4,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HPFQ, 4), was prepared, in which the nitrogen atom in position 1 carries a hydroxypropyl chain. The antiproliferative activity of HPFQ was studied in comparison with its analogue 1,4,6,8-tetramethylfuro[2,3-h]quinolin-2(1H)-one (FQ) and 8-methoxypsoralen (8-MOP). By incubation in the dark, HPFQ, although retaining antitopoisomerase II activity, appeared less effective than FQ. Upon UVA irradiation, HPFQ produced little amounts of singlet oxygen, but detectable levels of superoxide anion; like FQ, HPFQ induced numbers of DNA-protein cross-links, but no interstrand cross-links in mammalian cells. The HPFQ phototoxicity was comparable to that of FQ and 8-MOP, while mutagenic activity, scored in two Escherichia coli strains, seemed much less remarkable.

Cell Division↗
PubMedDate not supplied

Synthesis of angelicin heteroanalogues: preliminary photobiological and pharmacological studies.

A series of angelicin heteroanalogues, in which the furan was replaced by thiophene or a 1-substituted pyrazole moiety, was synthesised in order to obtain potential therapeutic agents with antiproliferative and/or other biological activities. In general, the antiproliferative activity of the new thioangelicin, tested in different biological substrates, appeared to be higher than that of the angelicin, the natural parent compound, but lower than that of 8-MOP, the furocoumarin ordinarily used in PUVA therapy and photopheresis. Thioangelicin 6 induced strong inhibition of T2 bacteriophage infectivity and was able to significantly repress the DNA synthesis in Ehrlich ascites cells and the clonal growth in HeLa cells. The pyrazolocoumarins did not show any noticeable effect upon UVA irradiation in all the biological systems considered. All the new angelicin heteroanalogues appeared to be free of the known phototoxicity of furocoumarins on the skin. The pyrazolocoumarins have also been tested as anti-inflammatory, analgesic, antipyretic, local anaesthetic, anti-arrhythmic and platelet anti-aggregating agents by standard procedures. In this class of derivatives, 10a showed good anti-inflammatory and antipyretic properties, while 9a and 11a showed significant local anaesthetic activity.

Animals↗
PubMedDate not supplied

Psoralen photosensitization of L 1210 leukaemia cells: an approach to a new combined therapy.

Psoralen photosensitization of L 1210 cells has a strong effect on DNA and RNA syntheses and this result appears connected with the psoralen photobinding to DNA. Protein synthesis is less sensitive and its inhibition seems due to a different photochemical interaction, very likely to the psoralen photobinding to RNA. A combined therapy using cyclophosphamide and L 1210 cells psoralen-photoinactivated was performed after the leukaemia transplant, showing a significant decrease in mortality, even in comparison with the simple treatment with the alkilating drug.

Animals↗
PubMedDate not supplied

T2 phage sensitization by linear and angular furocoumarins.

T2 bacteriophage sensitization has been studied using two furocoumarins capable of linking covalently to DNA to the same extent but producing different damages, psoralen and 4,5'-dimethylangelicin. Psoralen is a well-known linear furocoumarin capable of inducing in DNA both monoadducts and cross-links; 4,5'-dimethylangelicin is a new angular compound known as a pure monofunctional reagent. In the sensitization of T2 mature virions both drugs proved very active, yielding survival curves practically superimposable; on the contrary, in the experiments with the T2 vegetative form, i. e. its DNA inside the host, 4,5'-dimethylangelicin resulted much less effective, resembling the picture observed in the inactivation of the host bacteria. This result did not appear related to an enhancement of DNA repair by a Weigle effect. The different killing activity of 4,5'-dimethylangelicin can be explained supposing that this drug is capable of inducing cross-links in T2 DNA inside the virus core, in which it exists in a very folded form, but not in the same DNA after injection into the host bacteria.

DNA, Viral↗
PubMedDate not supplied

Effects of two different loading doses of L-tryptophan on the urinary excretion of tryptophan metabolites in rats, mice and guinea pigs. Correlation with the enzyme activities.

The effect of two different loading doses of L-tryptophan (0.5 and 1.0 g/Kg b.w.) on excretion of tryptophan metabolites and the relation to the enzyme activities were studied in rats, mice and guinea pigs. In rats there is no ratio between the dosage used and the levels of the metabolites excreted. Doubling the amount of tryptophan administered, a 5-fold increase in the elimination of the metabolites along the kynurenine pathway is obtained. The 1.0 g/Kg load provides a more complete pattern of the metabolites than with the 0.5 g/Kg b.w. load. Kynurenic acid, kynurenine and xanthurenic acid are the chief metabolites excreted. In mice, the urinary excretion of the metabolites is very low with both loads. In guinea pigs, xanthurenic acid is excreted in the highest amount and kynurenic acid and kynurenine also constitute the large fractions with both loadings. The load of 0.5 g/Kg b.w. is preferable to that of 1.0 g/Kg b.w. for not causing B6-deficiency. Liver tryptophan pyrrolase exists in two forms in rats, while in mice and in guinea pigs it is present only as holoenzyme. This enzyme is more active in rats than in the other two species of animals. Kynureninase activity is lower in guinea pigs, but it apparently correlated to the low levels of excretion of the metabolites following this step. Kynurenine aminotransferase is very active in rats and in mice, while it is apparently depressed in guinea pigs, in contrast with the high excretion of xanthurenic and kynurenic acids, that puts in evidence a B6-deficiency. The excretion of tryptophan metabolites and enzyme activities are better correlated in rats.

Animals↗
PubMedDate not supplied

Metabolites and enzyme activities involved in tryptophan metabolism in two different strains of mouse.

The urinary excretion of the tryptophan metabolites along the kynurenine pathway and the variations of enzyme activities involved in the degradation of tryptophan have been studied in two strains of mice. The total excretion of the metabolites was significantly higher in the strain of albino N.C.L. than in Swiss albino mice, in accordance with the higher activity of tryptophan pyrrolase, which was present only as holoenzyme. In both strains kynurenine, kynurenic and xanthurenic acids were excreted in larger amounts. However, the albino N.C.L. mice excreted a large amount of xanthurenic acid, not correlated with the slightly higher kynurenine aminotransferase activity observed in this strain. The very high excretion of this metabolite indicates that the load of tryptophan causes a B6-deficiency. Liver kynureninase activity was similar in both strains. Correlation between total urinary excretion of the tryptophan metabolites and enzyme activities appears in the same strain of mice, even though differences are present in different strains.

Animals↗