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Biomedical subjects

G Prodi

Publications and source records attributed to G Prodi.

At least 37 records · Page 2Linked to original sources
PubMed1985

Colony-stimulating activity from the new metastatic TS/A cell line and its high- and low-metastatic clonal derivatives.

We investigated the presence of colony-stimulating factor (CSF) in supernatants obtained from TS/A, a new metastatic murine cell line, and from its high-and low-metastatic clonal derivatives (E and F clones, respectively). TS/A cells produced a CSF in vitro that induced proliferation and differentiation of murine monocytic and granulocytic progenitors in agar cultures. In TS/A-bearing mice remarkable splenomegaly, blood granulocytosis and thymus depletion were observed along with a stimulatory activity in serum and a strong proliferative activity both in spleen and in bone marrow populations. Conditioned media from E clones showed an in vitro colony-stimulating activity greater than those of F clones. Mice injected subcutaneously with cells of all clones studied showed granulocytosis, splenomegaly and thymus depletion, although to varying degrees. However, no direct correlation between granulocytosis-splenomegaly and the number of spontaneous lung metastases was observed.

Animals↗
PubMed1985

The covalent binding of bromobenzene with nucleic acids.

The hepatotoxic compound bromobenzene binds to DNA, RNA, and proteins of rat and mouse liver in vivo. Binding to a significant extent is also detected in mouse kidney. The covalent binding index (CBI) of bromobenzene is comparable to CBI values of moderately oncogenic substances. The enzyme-mediated in vitro interaction of bromobenzene with calf thyumus DNA and synthetic polyribonucleotides is effected only by microsomes, especially those from mouse and rat liver. Microsomes from mouse lung are also efficient in bioactivating bromobenzene to interact with DNA. Among polyribonucleotides, poly(G) and poly(A) are the most labeled substrates. The suppression of binding to DNA by SKF 525-A and the induction of microsomal activity by a pretreatment with phenobarbitone in vivo confirm that bromobenzene is bioactivated by a P-450 dependent-microsomal mixed function oxidase system. The covalent binding can be the main event to determine the possible carcinogenicity by genotoxic mechanisms. Bromobenzene is photoactivated by ultraviolet light (lambda = 254 nm) to forms capable of interacting with DNA in vitro; the binding is linear up to time.

Animals↗
PubMed1985

Genotoxicity of 1,1-dichloroethane.

1,1-Dichloroethane is covalently bound to macromolecules of rat and mouse organs in vivo after ip injection. Covalent Binding Index is typical of initiators classified as weak carcinogens. In vitro binding of 1,1-dichloroethane to nucleic acids and proteins is mediated by liver P-450-dependent microsomal mixed function oxidase system. Lung microsomes are weakly efficient whereas kidney and stomach microsomal fractions are uneffective. Interaction with macromolecules is enhanced by pretreatment with phenobarbitone and suppressed by 2-diethyl-aminoethyl-2,2-diphenyl valerate. Cytosolic enzymes from all of tested organs do not catalyze binding to macromolecules. GSH and/or cytosol addition to microsomal system determine a decrement or suppression of binding extent. This fact suggests that GSH plays a detoxificant role in 1,1-dichloroethane metabolism as for some other chlorinated compounds occurs.

Animals↗
PubMed1985

In vivo and in vitro covalent binding of chlorobenzene to nucleic acids.

At 22 hr after ip injection into male Wistar rats and BALB/c mice, chlorobenzene was covalently bound to DNA, RNA and proteins of the liver, kidney and lung, as has been found with various weak carcinogens. A microsome-mediated interaction with DNA occurred in vitro. The interaction was enhanced by pretreatment in vivo with phenobarbitone but was suppressed by addition of 2-diethylaminoethyl-2,2-diphenylvalerate HC1 in vitro. These results indicate the involvement of cytochrome P-450. Liver microsomes were efficient bioactivators, whereas cytosol was ineffective. The extent of in vitro interaction of chlorobenzene with synthetic polyribonucleotides was of the same order as that with DNA. Finally, ultraviolet irradiation (lambda = 254 nm or lambda max = 365 nm) activated this environmental contaminant to forms capable of interacting with DNA. The results represent evidence for genotoxicity of chlorobenzene.

Animals↗
PubMed1985

In vivo reexpression of H-2 antigens in B16 melanoma cells.

We have previously shown that B16-A (H-2b) murine melanoma cells, when cultured in vitro for more than ten passages, have an undetectable or reduced expression of H-2Kb and Db antigens, respectively. We have now studied the possibility to restore H-2 expression (measured by quantitative antisera absorption) in B16-A cells either by a limited (30 days) period of in vivo growth or by treatment with immune interferon. In vivo transplants in allogeneic H-2k or H-2d mice and in H-2-compatible but Mls and multiple non-H-2 loci incompatible mice restored the normal expression of Kb and Db antigens. Cells obtained from tumors grown in syngeneic or in minor histocompatibility antigens-allogeneic mice showed only a weak increase in Db antigens. Such induction of H-2 expression appears to be mediated by the host's immune system, since (1) cells obtained from tumors grown in allogeneic BALB/c nude mice expressed much lower levels of H-2 antigens than those from tumors grown in normal BALB/c mice, and (2) it was possible to induce H-2 expression by growing B16 cells in syngeneic C57Bl/6 mice previously allostimulated with unrelated BALB/c tumor. In vitro treatment with immune interferon restored the expression of both Kb and Db antigens. We hypothesize that H-2 reexpression on B16 cells grown in allogeneic hosts could take place via the nonspecific components of the immune response, such as immune interferon.

Animals↗
PubMed1984

In vivo and in vitro binding of 1,2-dibromoethane and 1,2-dichloroethane to macromolecules in rat and mouse organs.

The comparative interaction of equimolar amounts of 1,2-dichloroethane and 1,2-dibromoethane with rat and mouse nucleic acids was studied in both in vivo (liver, lung, kidney and stomach) and in vitro (liver microsomal and/or cytosolic fractions) systems. In vivo, liver and kidney DNA showed the highest labeling, whereas the binding to lung DNA was barely detectable. Dibromoethane was more highly reactive than dichloroethane in both species. With dichloroethane, mouse DNA labeling was higher than rat DNA labeling whatever the organ considered: the opposite was seen for the bioactivation of dibromoethane. RNA and protein labelings were higher than DNA labeling, with no particular pattern in terms of organ or species involvement. In vitro, in addition to a low chemical reactivity towards nucleic acids shown by haloethanes per se, both compounds were bioactivated by either liver microsomes and cytosolic fractions to reactive forms capable of binding to DNA and polynucleotides. UV irradiation did not photoactivate dibromoethane and dichloroethane. The in vitro interaction with DNA mediated by enzymatic fractions was PB-inducible (one order of magnitude, using rat microsomes). In vitro bioactivation of haloethanes was mainly performed by microsomes in the case of dichloroethane and by cytosolic fractions in the case of dibromoethane. When microsomes plus cytosol were used, rat enzymes were more efficient than mouse enzymes in inducing a dibromoethane-DNA interaction: the opposite situation occurred for dichloroethane-DNA interaction, and this is in agreement with the in vivo pattern. In the presence of both metabolic pathways, addition or synergism occurred. Dibromoethane was always more reactive than dichloroethane. An indication of the presence of a microsomal GSH transferase was achieved for the activation of dibromoethane. No preferential binding in vitro to a specific polynucleotide was found. Polynucleotide labeling was higher than (or equal to) DNA binding. The labeling of microsomal RNA and proteins and of cytosolic proteins was many times lower than that of DNA or polynucleotides. The in vivo and in vitro data reported above give an unequivocal indication of the relative reactivity of the haloethanes examined with liver macromolecules from the two species and agree, on the whole, with the relative genotoxicity (DNA repair induction ability, mutagenicity and carcinogenicity) of the chemicals.

Animals↗
PubMed1984

In vivo and in vitro binding of epichlorohydrin to nucleic acids.

Epichlorohydrin (EC) binds to macromolecules of biological relevance in vivo: DNA is less labelled than RNA and proteins, rat organs interact more than mouse organs, stomach is the most labelled organ with liver, kidney and lung involved in decreasing order. Based on the Covalent Binding Index (CBI), EC is a weak-moderate oncogen, just as other chlorinated hydrocarbons such as 1,2-dichloroethane and carbon tetrachloride. An interaction of EC with nucleic acids (DNA and polyribonucleotides) occurs also in vitro. It is mediated either by chemical reactivity per se of the molecule (near-UV (NUV) irradiation does not photoactivate EC) and by enzymatic (microsomal and/or cytosolic) fractions, whose relative effectiveness is variable in relation to the organ tested. The best substrates for interaction are poly(G) and poly(A) when using microsomal and cytosolic fractions, respectively, whereas the labelling of double-stranded DNA is always lower. On the whole, the picture of enzyme (microsome + cytosol)-mediated in vitro interaction is similar to the pattern of in vivo binding, with the exception of rat stomach enzymes which are inactive in vitro.

Animals↗
PubMed1983

Induction of diphtheria toxin-resistant mutants in human cells by halogenated compounds.

The mutagenic power of 1,2-dichloroethane, 1,2-dibromoethane, 1,2-diiodoethane was tested in the human cell line, EUE. In our mutagenic system, based on selection against diphtheria toxin, the halogenated compounds, 1,2-dichloroethane and 1,2-dibromoethane revealed a strong mutagenic effect, whereas 1,2-diiodoethane was not mutagenic at a concentration allowing survival of 41%.

Cell Line↗
PubMed1983

Inverse relationship between anti-SV40 TASA and anti-H-2 cytotoxic responses.

The in vitro cytotoxic response against H-2d and H-2b SV40-transformed fibroblasts was studied in a 40-h 3H-proline assay. A very low response against SV40 TASA is associated with the H-2d antigens on target cells: however, SV40-transformed H-2d cells are as immunogenic as SV40-transformed H-2b cells and prime against H-2b target cells. The data concerning in vitro amplification of the anti-SV40 TASA response and the involvement of cyclophosphamide-sensitive suppressor populations confirm the comparable immunogenicity of SV40-transformed H-2d AND H-2b cells and cannot account for the haplotype-related behavior observed with SV40-transformed target cells. The study of the response against allogeneic SV40-transformed cells shows the reverse situation: the lower cytotoxic response is now associated with the H-2b antigens on SV40-transformed cells. As suggested by the data presented here, an interaction between SV40 TASA and H-2 antigens might be postulated.

Animals↗
PubMed1983

Effect of vitamin A palmitate on mutagenesis induced by polycyclic aromatic hydrocarbons in human cells.

The effect of vitamin A palmitate (VAP) on mutagenesis induced by polycyclic aromatic hydrocarbons (PAH) was examined in a human epithelial-like cell line (EUE). Cultures were exposed to benzo[a]pyrene (BP), 3-methylcholanthrene (MCA), 7,12-dimethylbenz[a]anthracene, with or without VAP, and mutation frequencies were determined by selection against diphtheria toxin. A strong inhibition of mutagenesis was observed particularly with MCA and BP. VAP, in the same cell line, reduced 3H-labeled PAH binding to DNA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Impaired H-2 expression in B16 melanoma variants.

We studied the expression of H-2b alloantigens in three different B16 melanoma lines cultures in vitro. Cell lines were B16-F1 and two cell cultures (named B16-A and B16-B) newly derived from two different in vivo sublines of B16 melanoma. The assays used were in vivo tumour growth in allogeneic (BALB/c and B10.BR) as compared to syngeneic mice, in vitro cell-mediated cytotoxicity by anti-H-2b immune lymphocytes and absorption of anti-H-2b antisera activity. The B16-F1 line was able to efficiently kill allogeneic hosts, could not be lysed by anti-H-2b cytotoxic effectors and did not express any serologically detectable amount of H-2b alloantigens. The B16-A line was H-2 positive during the early in vitro passages, then, at the 8th-10th passages, it acquired the capacity to kill allogeneic hosts, lost the sensitivity to anti-H-2b cytotoxic effectors and the H-2Kb antigens became undetectable The expression of H-2Db was reduced, although at a lower degree. Similar data were obtained with B16-B cells, which after 10 in vitro passages grew and killed allogeneic hosts, showed a decreased sensitivity to cytotoxic anti-H-2b effectors and a very low expression of the K region antigens. The results indicate that H-2 expression is altered in B16 melanoma lines and this may influence the different metastatic capacity of such cells.

Animals↗
PubMed1982

Glucocorticoid receptor and in vitro sensitivity to steroid hormones in human lymphoproliferative diseases and myeloid leukemia.

The glucocorticoid receptor (GR) quantitation by a whole-cell assay and/or cytosol technique and the in vitro sensitivity to steroids have been assessed in peripheral blood cells from normal donors and patients with chronic lymphatic leukemia (CLL), acute lymphoblastic leukemia (ALL), lymphosarcoma cell leukemia (LSCL), acute nonlymphatic leukemia (ANLL), and chronic myeloid leukemia (CML). Within the lymphoproliferative diseases, ALL cells exhibited the highest GR concentration (regardless of the method used) and the highest in vitro inhibition of spontaneous [3H]thymidine ([3H]TdR) uptake by glucocorticoids. A significant relationship between GR concentration (whole-cell assay) and in vitro sensitivity to dexamethasone was also found. On the contrary, CLL cells presented the highest sensitivity to glucocorticoids in PHA-stimulated cell cultures. Cells from the only two ALL patients who did not undergo a remission after glucocorticoid-inclusive chemotherapy had both the lowest in vitro sensitivity to dexamethasone and the lowest GR concentration with whole-cell assay. Concerning myeloid leukemia, ANLL patients had GR concentrations slightly higher than those found in the ALL group but exhibited the lowest degree of inhibition of spontaneous [3H]TdR uptake by dexamethasone (stimulatory effects occurred in some cases). CML cells exhibited an inhibition degree by in vitro glucocorticoids significantly higher than that of ANLL cells but not different from that of lymphoproliferative diseases. No clear relationship among GR pattern, in vitro cell sensitivity to glucocorticoids, and clinicohematologic parameters was observed in myeloid leukemia-bearing patients.

Adult↗
PubMed1981

The occurrence of multiple steroid hormone receptors in disease-free and neoplastic human ovary.

The cytoplasmic receptors for 17 beta-estradiol (ER), 5 alpha-dihydrotestosterone (AR), progesterone (PR), and cortisol (GR) have been quantified in 36 specimens from the human ovary (13 disease-free, 5 benign, and 18 malignant) by a dextran-coated charcoal (DCC) technique. The occurrence of receptor-positive biopsies were: ER 46%, AR 85%, PR 54%, GR 92%, in normal tissue; ER 40%, AR 100%, PR 20%, GR 50%, in benign tumors; and ER 67%, AR 72%, PR 50%, GR 88%, in malignant lesions. Furthermore, the simultaneous occurrence of ER and PR in malignant tumors was 50% yet all four receptors were found to be present only in 44% of the cases. The findings reported here on the strong correlation existing between ER and PR presence or amount agree with previous observations on normal and neoplastic specimens from human breast and endometrial tissues.

Carcinoma↗
PubMed1981

DNA damage by haloalkanes in human lymphocytes cultured in vitro.

The DNA damaging activity of 7 haloalkanes was studied in a short-term in vitro system which utilized human lymphocytes. The parameters studied were the inhibition of scheduled (duplicative) and unscheduled (reparative) DNA syntheses seen as tritiated thymidine uptake. The results obtained suggested that chloromethyl methyl ether (CMME), 1,2-dibromoethane (DBE), trichloroethylene (TCE) and 1,2-dichloroethane (DCE) gave positive results such as DNA damaging agents, while carbon tetrachloride (CTC), chloroform (TCM) and dichloromethane (DCM) gave low or negative results.

Carbon Tetrachloride↗
PubMed1981

Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light.

Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency (less than 8 x 10(-6)). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTr) mutants up to 1000-fold. The maximum recovery of DTr mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages.

Cell Line↗