Trifluoromethylanilines--their effect on DNA synthesis and proliferative activity in parenchymal organs of rats.

Reactive isomeric 3- and 4-trifluoromethylanilines (3-,4-TFMA), and control aniline itself, induced the following effects on biosynthesis of DNA in the liver, kidney, thymus and spleen of rats: (a) The administration of 4-TFMA initially suppressed the utilization of labeled thymidine for splenic DNA synthesis during the early prereplicative stage. However, with progressing time the incorporation of the labeled marker began to increase and in 30 h its level exceeded the controls by more than 200%. As expected, aniline administration resulted in mild depression of incorporation during the whole period studied.

The binding spectra of rat renal and hepatic microsomal cytochromes P-450 with cyclosporine A.

Binding difference spectra of rat renal and hepatic cytochromes P-450 with cyclosporine A (CsA) were measured. In both cases reversed type I spectra were found with the absorbance maximum at 416 nm and minimum at 378 nm. Apparent spectral dissociation constant Kd and maximal absorbance difference delta Amax416-378 did not change substantially with the concentration of the CsA stock solution used.

The effect of lentinan on proliferative processes in parenchymal organs of rats--I. The effect on pyrimidine and nucleic acid syntheses.

The present study investigated the effect of Lentinan on the biochemical events associated with the pyrimidine and nucleic acid syntheses in the liver, kidney, thymus and spleen of rats. Lentinan was used at a dose of 4 mg/kg/day (twice) and in a single dose of 20 mg/kg. The following changes were observed.

Effect of 3,7-bis-(4-trifluoromethylphenyl)-1,5,3,7-dioxadiazocane on pyrimidine and DNA synthesis in rat organs.

The administration of the lipophilic 3,7-bis-(4-trifluoromethylphenyl)- 1,5,3,7-dioxadiazocane (TFMPD) to rats induced the following effects on the biosynthesis of DNA in the liver, kidney, thymus and spleen: (a) The utilization of [3H]thymidine for the synthesis of liver DNA thymine was decreased after the administration of a single dose of the drug. The depression of the specific activities of DNA pyrimidines of liver DNA in experimental groups was observed also after an injection of [14C]orotic acid. (b) A decreased incorporation of labeled thymidine had occurred also in the spleen during the prereplicative period.

The effect of cyclosporine A on renal and hepatic microsomal mixed function oxidase systems in rats.

The effect of cyclosporine A (CsA), the immunosuppressant used in transplantation and also in the treatment of some autoimmune diseases, on the microsomal mixed function oxidase (MFO) systems in rat kidney and liver was studied. Since CsA given intragastrically (50 mg/kg/day) for three consecutive days decreased body, liver and kidney weights, in rats, the results were compared not only with the control untreated animals but also with the group of fully starved rats. In the liver the cytochrome P-450 level and aniline-hydroxylase activity were slightly higher than in the control rats but not as high as in the fully starved animals.

Alterations of pyrimidine and nucleic acid synthesis during adaptive growth of liver induced by nafenopin, a peroxisome proliferator. An in vivo study.

The de novo synthesis of pyrimidine nucleotides in the rat liver after administration of nafenopin (NFP) was studied with the aid of [14C]orotic acid; the utilization of preformed nucleosides (salvage pathways) was followed using the [14C]cytidine and [14C]thymidine. A single dose (400 mg/kg) as well as repeated doses (100 mg/kg/day) of NFP increased the concentration of the cytidine and uridine components of the acid-soluble extract (ASE) of rat liver. Increase in the concentration of the cytidine components preceded the increase in the uridine components.

Effect of nafenopin and clofibrate on uptake and utilization of labeled thymidine for DNA synthesis in rat liver and kidney.

The mitogenic effect of nafenopin and clofibrate in the liver is paralleled by a decreased utilization of [14C]thymidine for kidney DNA synthesis. Analogous changes in the liver and kidney DNA biosynthesis after nafenopin administration occur if [14C]orotic acid is added as a precursor of DNA pyrimidines. There is a time correlation between the uptake of labeled thymidine and its utilization for DNA synthesis in the liver during the initial stages of the mitogenic effect of the drug.

Effect of clofibrate on DNA synthesis in rat liver and kidney.

A single dose of clofibrate (400 mg/kg), given to rats, increased the incorporation of (3H)thymidine into liver DNA, in a period of 20-30 h after administration. However, (3H)thymidine incorporation into hepatic DNA of rats treated repeatedly was identical to that of control animals. After the administration of a single dose of clofibrate a small increase in (3H)thymidine incorporation also occurred in kidney DNA; repeated doses, however, resulted in a marked suppression of labeling.