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C Bolognesi

Publications and source records attributed to C Bolognesi.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Genotoxic damage in subjects exposed to automobile exhaust: preliminary results].

The associations between selected biomarkers of biologically effective dose (32P-post-labelling-DNA adducts), early biological effects (Micronuclei, MN) and sister chromatid exchanges (SCE) and individual measurements of exposure to benzo(a)pyrene (a surrogate index of exposure to polynuclear aromatic hydrocarbons, PAHs) are investigated in a study being conducted among traffic police workers and referent subjects in the City of Genova, Italy. Preliminary findings show B(a)P mean values of 1.33 ng/m3, SD = 1.35 ng/m3 and 0.06, SD = 0.17 in traffic police workers and referent subjects, respectively. Micronuclei mean levels in peripheral blood lymphocytes of 26 traffic police workers and 25 referents were 3.30, DS = 1.24 e 3.90, DS = 1.50 (per 1,000 binucleated cells). Eleven subjects (61%) out of 18 had detectable levels of DNA adducts (32P-post-labelling technique, range 1.8-9.0 Relative Adduct Level (RAL) per 10(9) nucleotides).

Adult↗
PubMed1995

Influence of sex on cytogenetic end points: evidence from a large human sample and review of the literature.

The planning and evaluation of human cytogenetic studies should contemplate various confounders and effect modifiers, among these, sex and sex-related factors. The association between this variable and cytogenetic damage has been extensively studied, but conclusive evidence has thus far not been reached, especially for the most recent assays, such as the micronucleus test (MN). In the attempt to quantitatively estimate the sex effect on sister chromatid exchange (SCE), chromosomal aberration (CA), and MN in peripheral blood lymphocytes, we reanalyzed the original data sets of several biomonitoring studies performed over the last decades in 10 Italian laboratories. This approach yielded a very large database, namely 2140, 2495, and 2131 subjects screened for SCE, CA, and MN, respectively. Differences between sexes were expressed in terms of relative risk (RR) of females versus males, after adjustment for age, smoking habits, occupation exposure and inter- and intralaboratory variation. No difference between sexes was found for the frequency of SCE [RR = 1.01; 95% confidence interval (CI) = 0.99-1.03] and CA (RR = 1.00; 95% CI = 0.92-1.08) even if the CI of the RR for SCE includes the 3% excess in females frequently reported by the literature. Conversely, a 29% overall increase of the MN rate in females was observed in the whole data set (RR = 1.29; 95% CI = 1.20-1.38). Different trends by age of the MN rate are described in the two sexes, focusing on the peak observed in females in the menopausal period and on the subsequent decrease.

Adult↗
PubMed1994

Chemical hazard evaluation: the use of factual health and safety databanks.

The usefulness of factual health and safety databanks is discussed in this paper. Four databanks have been selected for this study: HSDB (Hazardous Substances Data Bank), ECDIN (Environmental Chemicals Data Information Network), RTECS (Registry of the Toxic Effects of Chemical Substances) and CCRIS (Chemical Carcinogenesis Research Information). The quality of the information available in the databanks considered was examined for five different chemical compounds and the completeness of the information available was carried out by an analysis of carcinogenic and mutagenic data.

Animals↗
PubMed1994

Genotoxic effects of the carbamate insecticide methomyl. I. In vitro studies with pure compound and the technical formulation "Lannate 25".

The carbamate insecticide methomyl and the methomyl-containing technical formulation "Lannate 25" were tested on whole blood human lymphocyte cultures. Both products induced dose-dependent increases in chromosome aberrations and micronuclei. Lannate 25 induced DNA damage as measured by the alkaline elution assay and hydroxylation of guanine at the C8 position. Sister chromatid exchanges were not increased significantly with either product. Overall, the technical formulation was more active than the pure compound, when compared at similar concentrations of active principle. Moreover, a different ratio of CREST-positive/CREST-negative micronuclei was observed with the two products, pure methomyl being relatively more active than Lannate 25 in the induction of CREST-positive micronuclei. On the basis of these results, previous evaluations of methomyl as a nongenotoxic compound should be reconsidered.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Genotoxic effects of the carbamate insecticide, methyomyl. II. In vivo studies with pure compound and the technical formulation, "Lannate 25".

The carbamate insecticide, methomyl, and the methomyl-containing technical formulation, "Lannate 25", were tested for the induction of DNA damage in vivo. Swiss CD1 mice were treated intraperitoneally with test substances and the following tests were performed: alkaline elution of liver and kidney DNA, 8-hydroxyguanosine detection in liver DNA, and 32P-postlabelling analysis of DNA adducts in liver DNA. The clastogenic activity of the two pesticide preparations was also evaluated as micronucleus frequency in bone marrow. No DNA adducts were detected in liver DNA of mice treated with pure methomyl, while a dose-related increase in DNA adducts was found in Lannate 25-treated animals. All other tests were positive with both methomyl and Lannate 25. A summary of genotoxic activity of methomyl is also presented. The hypothesis that the observed genotoxic effects of methomyl are induced indirectly, through formation of active oxygen species, is discussed.

Animals↗
PubMed1993

Biomonitoring of workers exposed to pesticides.

The potential clastogenic effects of pesticides was investigated in 71 floriculturists exposed to complex chemical mixtures. Exposed and referent subjects were selected from the same geographical area located in north western Italy. A significant association between micronuclei frequency and occupational exposure to pesticides was found (RR = 1.25). A positive dose-response gradient was observed with years of employment (used as an index of cumulative exposure) as a floriculturist. Individuals working exclusively in greenhouses (confined spaces) showed higher micronuclei levels than subjects working in open fields. The study supports the hypothesis that human exposure to pesticides causes a clastogenic damage.

Agriculture↗
PubMed1993

Cytogenetic analysis of a human population occupationally exposed to pesticides.

A great deal of the flower cultivation in Italy is carried out in the western part of the Region of Liguria. The extensive use of pesticides professionally exposes floriculturists operating in this area to a complex mixture of compounds. The frequency of micronuclei in peripheral lymphocytes has been evaluated in 71 floriculturists and in a control group of 75 healthy blood donors living in the area. No correlation between age and micronucleus frequency was found in peripheral lymphocytes of the controls while an increase in this parameter was observed in the elderly of the exposed group. Our data suggest a sex-related effect in the induction of micronuclei. The frequencies of micronucleated lymphocytes were significantly higher in females than in males in both exposed and control groups (RR = 1.45, 95% C.I. 1.25-1.67). The main result of this study, however, is the observation of a significant increase in micronucleated lymphocyte frequency in people occupationally exposed to pesticides. The micronucleus frequency was 8.57/1000 for exposed persons and 6.67/1000 for controls (p < 0.05). A dose-response relationship with duration of exposure was apparent with a maximum increment of 71% in the frequency of micronuclei in subjects exposed for over 30 years.

Adult↗
PubMed1993

Relationship between poly(ADP-ribose) polymerase activity and DNA damage induced by zinc dithiocarbamates in mouse and rat liver.

The genotoxic effects due to in vivo treatment with zinc dithiocarbamates were evaluated in rat and mouse liver. The two pesticides Zineb and Ziram, belonging to this chemical class, induced an increase in single-strand DNA breaks, as measured by the alkaline elution technique. The nuclear enzyme poly(ADP-ribose) polymerase (pADPRP), a chromatin-bound catalytic protein, utilizing NAD+ as a substrate, was tested by a radiometric procedure. A close relationship between the increased extent of DNA damage and the enhanced level of endogenous pADPRP activity was obtained in rat liver, whereas both parameters remained unchanged in mouse liver.

Animals↗
PubMed1991

DNA damage induced by 7,12-dimethylbenz[a]anthracene in the liver and the mammary gland of rats exposed to polycyclic aromatic hydrocarbon enzyme inducers during perinatal life.

The long-lasting modulating effect induced by the prenatal or neonatal exposure to phenobarbital (PB) and aroclor on the genotoxic activity of 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats was studied. The effect was measured as DNA damage evaluated in the liver and in the mammary gland of 55-day-old animals, 4 and 24 h after an i.g. injection of 80 mg/kg of DMBA. PB was given per os, i.g. or in drinking water to pregnant females and by i.g. only to neonates or in adult progeny. Aroclor was injected i.g. in prenatal and in neonatal life, and a second dose was given in adult life. Under these experimental conditions it was shown that DNA damage kinetics caused by DMBA are modulated by exposure to PB and, to a minor extent, by aroclor. The amount and persistence of DNA damage were highest when PB was administered to neonates. An average 2-fold increase in the elution constants (K) of DNA in the liver and the mammary gland was observed 4 h after DMBA treatment, as compared to uninduced animals. Repeated enzyme induction by PB seems to reduce DMBA genotoxicity, as shown by a decrease in DNA damage and persistence in the liver and mammary gland. The inducibility of the monooxygenase enzyme system in perinatal life favouring metabolic activation or inactivation of polycyclic aromatic hydrocarbons might be critical in determining individual susceptibility of adult progeny to chemical carcinogenesis by DMBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

[Induction of micronuclei in polychromatic erythrocytes from mouse bone marrow following intraperitoneal administration of halogenated benzenes].

The mutagenicity of halogenated benzenes, including three isomers of tri- and tetrachlorobenzenes (TCB, TeCB) was studied on male Swiss CD1 mice by MN test. The data presented show that all the halogenated benzenes tested were found to be clastogenic apart from 1,2,3,5-TeCB. No significant differences were observed in the clastogenic activities of TCB-isomers and TeCB-isomers.

Animals↗
PubMed1988

A new method to reveal the genotoxic effects of N-nitrosodimethylamine in pregnant mice.

DNA damage and repair in kidney and liver of mouse fetuses exposed to selected doses of N-nitrosodimethylamine (NDMA) (CAS No. 62.75.9) were studied using the alkaline elution technique. CD1 female mice (15 days pregnant) were treated i.p. with 2 and 10 mg/kg b.w. of NDMA; a slight increase in DNA damage was observed in their fetuses compared to untreated controls. A 2-fold higher extent of DNA damage was induced when mice were treated by intrafetal injections of a rat S9 activating fraction (S9) immediately before exposure to the same dose of NDMA by transplacental means. The DNA-strand breaks disappeared as a function of time in animals treated with NDMA alone. In contrast, a significant persistence of DNA damage was detected in the liver and lung of fetuses which were treated with S9 and NDMA in sequence. These experiments demonstrate the metabolic immaturity of unborn mice as far as the carcinogenic activation of NDMA is concerned and show the high susceptibility of fetal tissues to DNA-damaging agents. The alkaline elution applied in vivo by the transplacental route combined with the intrafetal injection of an exogenous activating microsomal fraction allow to extend our knowledge on the interaction of metabolism-dependent chemicals with fetal tissues.

Animals↗
PubMed1988

Target tissue DNA damage in inbred mouse strains with different susceptibility to the colon carcinogen 1,2-dimethylhydrazine.

We have compared liver, kidney and colon DNA damage, as single strand breaks, in mice with different strain-dependent susceptibility to the colon-specific carcinogen 1,2-dimethylhydrazine (DMH). The mouse strains studied were: AKR/J, DBA2 totally resistant; CD1, C57BL/6N moderately susceptible; SWR/J very susceptible to DMH-induced carcinogenesis. DNA breaks were estimated from the elution rate constant (K) according to the alkaline elution technique. At 4 h after carcinogen administration a substantial and comparable DNA damage was found in liver and kidney in all the strains examined. The DNA fragmentation index, however, reached a maximum value at 2 h after treatment in the liver of the most susceptible strain (SWR/J). About 50% of the liver DNA damage detected in all five strains 4 h after DMH administration persisted at 24 h after treatment and was totally repaired at 72 h. Kidney DNA damage decreased in 48 h toward the range of control values. In colon epithelial cells (the carcinogen target tissue) 2 and 4 h after DMH administration the amount of DNA single strand breaks was correlatable with the strain sensitivity to the carcinogen. In the time interval studied (2-72 h after DMH administration) the decrease of colon DNA damage was linear in the resistant strains. In contrast, in the more susceptible strain (SWR/J), the amount of DNA breaks remained high up to 24 h after treatment and returned to background level at 72 h.

1,2-Dimethylhydrazine↗
PubMed1987

Specific targets of alkylating agents in nuclear proteins of cultured hepatocytes.

We have established a specific correlation between the carcinogenic potency of a series of alkylating agents, with a mechanism of reaction ranging between Ingold's SN1-SN2 (ENU greater than MNU = MNNG greater than EMS greater than DMS = MMS) (Vogel et al., 1979; Bartsch et al., 1983) and specific target sites in the amino acids of nuclear proteins of cultured hepatocytes. More potent carcinogens, that react predominantly with an Ingold's SN1 mechanism, mainly alkylate the amino group of lysine and the guanido group of arginine. Weaker carcinogens, reacting with a mechanism closely resembling an Ingold's SN2, mainly alkylate the sulfhydryl group of the cysteine and the 3 position of the imidazolic ring of histidine. A compound with an intermediate type of reactivity alkylates, to a comparable extent, all 4 of the above-described positions. Although stable DNA damage brought about by alkylating carcinogens is considered to be the most likely cause of neoplastic transformation, epigenetic modifications may also play an important role in the process, especially because of their extreme stability. We have verified the existence of a linear correlation between the Swain-Scott substrate constant (S) of each compound and the amount of alkylation produced at the specific target sites. This type of correlation could be the basis of a 'short-term' genotoxicity assay in a battery of complementary tests.

Alkylating Agents↗
PubMed1986

In vitro DNA and nuclear proteins alkylation by 1,2-dimethylhydrazine.

The methylating carcinogen 1,2-dimethylhydrazine (DMH) CAS 540.73.8 is highly organ-specific and, under certain experimental conditions, produces a high incidence of adenocarcinoma in the colon of rodents. We have tried to assess the possibility that part of the organ-specifity in the carcinogenic effect of DMH could be attributed to its metabolism by specific microsomal enzymes. In particular, we compared the in vitro effects of DMH in the presence of either colon or liver microsomes from animals that had been treated with microsomal enzyme inducers. V79 Chinese hamster cells were used as the target to evaluate the damage to the genetic material, as judged by (1) formation of adducts of DNA bases and (2) amino acid modifications in nuclear proteins using [Me-14C]DMH and appropriate analytical detection systems. Our results tend to support the above postulated hypothesis.

1,2-Dimethylhydrazine↗
PubMed1986

Correlation between incidence of 1,2-dimethylhydrazine-induced colon carcinomas and DNA damage in six genetically different mouse strains.

Mice from strains with different susceptibility to the colon-specific carcinogen 1,2-dimethylhydrazine (DMH) were tested for DNA damage in liver, kidney and colon after administration of the compound at a dosage that has been reported to induce a high incidence of adenocarcinoma in the colon of rodents. DNA breaks were evaluated from their elution rate constant according to the alkaline elution technique. We found that 4 h after administration of the carcinogen there was a substantial and comparable DNA damage in liver and kidney of all strains examined. Conversely, colon DNA damage was hardly above control levels in the carcinogen-resistant strains. The highest DNA damage was detected in the most susceptible strain and was slightly lower in the two other susceptible strains. We propose that the extent of DNA breakage in a target organ could be one of the factors determining organ-specific and strain-specific susceptibility to DMH.

1,2-Dimethylhydrazine↗