Search PubMed⌕ Search

Biomedical subjects

S Grilli

Publications and source records attributed to S Grilli.

At least 91 records · Page 5Linked to original sources

17 beta-estradiol, 5 alpha-dihydrotestosterone, progesterone and cortisol receptors in normal and neoplastic human endometrium.

Using the value of 0.24 fmoles/microgram DNA as breaking point between high and low binding capacities, we quantified receptors for 17 beta-estradiol (ER), 5 alpha-dihydrotestosterone (DHTR), progesterone (PR) and cortisol (CR) in normal and neoplastic human uterine tissues. Concerning receptors occurrence, significant relationships were observed between ER and PR, ER and DHTR, and DHTR and PR. A direct correlation between the presence of ER and tumor grading was found: PR was less frequent in grade II and absent in grade III endometrial carcinoma, however this was not a significant correlation. In endometrial carcinoma at least 1 of the receptors was detected in 67-91% of the cases, 3 receptors (ER, DHTR, PR) in 56%, and all 4 receptors in 45%. The simultaneous detection of multiple receptors could play an important role in determining hormone response.

Aged↗

In vivo DNA repair after N-methyl-N-nitrosourea administration to rats of different ages.

DNA repair time-course was studied after injury by N-methyl-N-nitrosourea (MNU) in rat liver cells of animals of different ages and in fetuses using hydroxyurea (HU) as inhibitor of scheduled DNA synthesis. DNA repair was a rapid phenomenon, more so in young adults than in newborns, and was not detectable in fetuses. A correlation seems to exist among organ sensitivity to carcinogen, age of animal and DNA repair.

Age Factors↗

In vivo reaction of dimethylnitrosamine with nucleic acids.

7-Methylguanine is the main compound resulting from in vivo interaction between dimethylnitrosamine (DMNA) and nucleic acids, detected after strong acid hydrolysis. However, enzymic and alkaline hydrolysis of nucleic acids leads to quantitative liberation of methylamine. Methylamine isolated from liver nucleic acids of 15N-DMNA-treated rats has molecular weight of 31, thus demonstrating that DMNA-nitrogen is not involved in the binding.

Animals↗

Compared effects of N-hydroxyurethan, urethan and hydroxyurea on DNA synthesis. In vivo and in vitro studies.

The effect of N-hydroxyurethan (HUR) on DNA synthesis has been tested both in vivo on various tissues and in vitro on concanavalin A (ConA)-stimulated rat thymocytes and compared with the action of urethan and hydroxyurea. HUR suppresses scheduled DNA synthesis, except that of non-stimulated spleen cells in vitro. The inhibition is efficient and rapid and takes place immediately if the drug is administered at the peak of the S-phase. UR inhibits DNA synthesis in vitro only at much higher doses and with different time course. It is effective or slightly effective if it is administered at the peak of the S-phase. A conversion of urethan into HUR the latter depressing DNA synthesis could partly explain the differences observed. No toxicity was found after treatment with drugs at the concentration employed. Finally, the relationships between drug doses and cell responses have been particularly observed in vivo.

Animals↗

Cytoplasmic receptors for 17 beta-estradiol, 5 alpha-dihydrotestosterone and progesterone in normal and abnormal human uterine tissues.

Determinations of specific cytoplasmic receptors for 17 beta-estradiol (E), 5 alpha-dihydrotestosterone (DHT) and progesterone (P) in normal and abnormal endometrium are reported. The standardization of methodology with particular emphasis on specificity trials is outlined. Receptors were present in all but one case, a moderately differentiated endometrial adenocarcinoma. Generally speaking, steroid and peptide hormone plasma content in patients with malignant conditions were at the lower limit values of normal, except for follicle-stimulating hormone which had values significantly higher than normal. The question of E competition with DHT in binding DHT-receptor and the therapeutic implications of P-receptor estimation are discussed.

Adult↗

An in vitro study on the interaction between dimethylnitrosamine and nucleic acids via a microsomal system.

Radioactive alkylated bases, ribose or phosphate, were never found either in acid and alkaline hydrolysates of polyribonucleotides or in alkaline hydrolysates of DNA after incubation with 14C-dimethylnitrosamine (DMNA) in a microsomal system. Two radioactive compounds, which were co-chromatographed with methylamine and N-methylhydrazine, respectively, on column, paper, and thin-layer, were always detected. They differed from the compound derived from 7-methylguanosine after the alkali-mediated fission of the imidazole ring in its molecule. The in vitro system employed well represents the in vivo situation (7-methylguanine which is liberated from DNA after acid hydrolysis); however, it has given results which do not agree with the generally-accepted mechanism of DMNA alkylation at the N-7 position of guanine.

Animals↗

Effect of urethan on the synthesis of nucleic acids in thymus, spleen, and bone marrow.

Urethan, in a single dose of 1 mg/g body weight, exerts a strong inhibitory effect on DNA synthesis in lymphoid organs and bone marrow of rat. The inhibition observed in spleen and thymus is longer lasting than that exerted on bone marrow or regenerating liver, demonstrating a marked sensitivity of lymphoid cells to the drug. This effect can explain the rapid reduction of weight and cell number in thymus and spleen under urethan treatment, in absence of any lymphocytolytic action. The different effect of urethan on the different subpopulations of lymphoid cells therefore appears to be due to their kinetics rather than to a specific sensitivity of some of them.

Animals↗

Non-enzymatic and microsome-dependent binding of poly-cyclic hydrocarbons to DNA and polynucleotides.

The binding of tritium-labeled 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (BP) and 3-methylcholanthrene (MCA) to DNA or polynucleotides in vitro was re-examined both in the presence and in the absence of rat liver or human placental microsomes. A high level of non-enzymatic binding was evident when thymus DNA was used as acceptor. This non-enzymatic binding made it difficult to determine the effect of microsomes, except in the case of BP when induced rat microsomes were used. Better results were obtained using polynucleotides: a definite microsome-dependent binding occurred between all the polynucleotides and all the hydrocarbons tested. No clear evidence of binding catalysed by microsomes from human placenta was found except in polynucleotide-BP interactions: further studies are required to completely evaluate the ability of such nucleic acid-microsomal system for testing in vitro possible oncogenic substances in animals and humans.

9,10-Dimethyl-1,2-benzanthracene↗

The binding of dimethylnitrosamine to nucleic acids catalyzed by liver enzymic fractions.

The in vitro binding of a metabolite of dimethylnitrosamine (DMNA) to calf thymus DNA catalyzed by a microsomal system from rat liver is reported. The amount ob binding is unaffected by using microsomes induced by 3-methylcholanthrene and/or normal or induced pH 5 enzymes. The microsomal system is also effective in catalyzing covalent binding of the nitroso compound with synthetic polyribonucleotides.

Animals↗

Identification of dimethylnitrosoamine metabolites in vitro.

The incubation of dimethylnitrosoamine (DMNA) in the presence of rat liver microsomes leads to production of formaldehyde, formic acid, methylamine, and N-methylhydrazine. When pH 5-enzymes are added to the medium there is also the formation of N-methylhydroxylamide and N,N-dimethylhydrazine. The last compound is the only metabolite produced, to a lesser extent, by the pH 5-enzymes. Thus, the denitrosated or non-denitrosated metabolites are produced either by an oxidative dealkylation and by a reduction of DMNA, catalysed by microsomal and cellular soluble enzymes.

Animals↗

Degradation of dimethylnitrosoamine catalysed by physical and chemical agents.

Decomposition of dimethylnitrosoamine (DMNA) by chemical and physical agents was further investigated. Both photoirradiation with sunlight or ultraviolet ray and reductive reactions under acid conditions (likely occurring in the stomach) led to the formation of formaldehyde, formic acid, and N-methydrazine, in addition to denitrosated compounds such as methylamine, dimethylamine, and N-methylhydroxylamine. N-Methylhydrazine was the only compound which was not detected by photoirradiation under neutral conditions. The agreement between physiochemical and metabolic degradation products and the possible biological meaning are discussed together with the problem of environmental contamination by the nitroso compound.

Dimethylnitrosamine↗