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Biomedical subjects

R Benigni

Publications and source records attributed to R Benigni.

At least 73 records · Page 4Linked to original sources
PubMed1988

Induction of chromosome malsegregation by halogenated organic solvents in Aspergillus nidulans: unspecific or specific mechanism?

Three chloromethanes (dichloromethane, chloroform and carbon tetrachloride) and 8 chlorinated ethanes (1,1- and 1,2-dichloroethane, 1,1,1- and 1,1,2-trichloroethane, 1,1,1,2- and 1,1,2,2-tetrachloroethane, pentachloroethane and hexachloroethane) were assayed in tests for the induction of mitotic segregation in Aspergillus nidulans diploid strain P1. Eight of the 11 compounds assayed (dichloromethane, chloroform, carbon tetrachloride, 1,1- and 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,1,2- and 1,1,2,2-tetrachloroethane) significantly increased the frequency of morphologically abnormal colonies which produced euploid whole-chromosome segregants (haploids and non-disjunctional diploids). Only in one case (1,1,1,2-tetrachloroethane) was a borderline increase in crossing-over frequency observed, thus suggesting the involvement of non-DNA targets in aneuploidy induction by these chlorinated hydrocarbons. Conclusive evidence for the induction of aneuploidy as the primary genetic event was provided by experiments in haploid strain 35 with 1,2-dichloroethane and 1,1,1,2-tetrachloroethane. Mutagenic, lethal and growth-arresting activities were quantitatively estimated and compared to a series of descriptors of physical and chemical properties of the molecules by means of multivariate statistical analysis. Lipophilicity, known to be related to c-mitotic activity, did not show any significant relationship with aneuploidizing activity, whereas a possible correlation among physico-chemical descriptors and toxic properties of test chemicals was highlighted.

Aneuploidy↗
PubMed1988

Computer-assisted analysis of interlaboratory Ames test variability.

The interlaboratory Ames test variability of the Salmonella/microsome assay was studied by comparing 12 sets of results generated in the frame of the International Program for the Evaluation of Short-Term Tests for Carcinogens (IPESTTC). The strategy for the simultaneous analysis of test performance similarities over the whole range of chemicals involved the use of multivariate data analysis methods. The various sets of Ames test data were contrasted both against each other and against a selection of other IPESTTC tests. These tests were chosen as representing a wide range of different patterns of response to the chemicals. This approach allowed us both to estimate the absolute extent of the interlaboratory variability of the Ames test, and to contrast its range of variability with the overall spread of test responses. Ten of the 12 laboratories showed a high degree of experimental reproducibility; two laboratories generated clearly differentiated results, probably related to differences in the protocol of metabolic activation. The analysis also indicated that assays such as Escherichia coli WP2 and chromosomal aberrations in Chinese hamster ovary cells generated sets of results within the variability range of Salmonella; in this sense they were not complementary to Salmonella.

Analysis of Variance↗
PubMed1987

The conceptual framework of monitoring mutagens/carcinogens: a critical appraisal.

The main theme of this paper is an analysis of the present knowledge and conceptual framework in the field of monitoring for carcinogenic and mutagenic agents. The conclusions of the International Symposium on "Monitoring human exposure to carcinogenic and mutagenic agents" (Helsinki, 1983) were taken as a starting point for a series of considerations; methods suitable for the quantitative treatment of the information were applied to evidence the profile of current research in this area. The analysis indicated that the major underlying paradigms were related to technical considerations, such as chemical specificity, precision, reproducibility or ease of execution, as well as to the concept of mechanism of action of genotoxic agents. On the other hand, the lack of reliable information about the operational relevance of the systems for assessing health effects was dramatically evidenced. As a conclusion, the dangers of relying on a scientific background derived only from the basic research, without a critical re-examination in terms of real, operational performances of the systems, are emphasized.

Carcinogens↗
PubMed1986

A new insight into chemical mutagenesis by multivariate data analysis.

Computerized data analysis was applied to a genotoxicity data base, consisting of 42 chemicals assayed in 20 short-term mutagenicity tests. Factor and cluster analysis were used to elicit underlying patterns and to classify the chemicals in groups homogeneous for the kind of genetic damage induced. This analysis put in light a clear differentiation between effects in in vivo and in vitro systems, while the heuristic value of the traditional categories (such as point-mutation and chromosomal damage, or prokariotic and eukariotic systems) was not confirmed.

Humans↗
PubMed1986

The Second International Collaborative Study on Comparative Mutagenesis re-visited: analysis by multi-variate statistical methods.

Computerized data analysis methods were applied to a selected subset of the results generated by the International Program on Chemical Safety Collaborative Study on In Vitro Assays. The rationale of this study was the analysis of test performances and the comparison with the conclusions of a similar analysis previously performed on the results of the First International Study. The multi-variate data analysis techniques used in the present work proved to be particularly suitable for looking at the complex field of comparative mutagenesis in a logical and systematic fashion, and generated a clear classification of the assays on the basis of their experimental performances. This classification proved not to be consistent with the traditional categories that group tests according to genetic end-point and phylogenetic position, and afforded classes of assays distinct for their sensitivity and specificity in respect to carcinogens. In particular, two systems (Saccharomyces cerevisiae XV185-14C mutation and Syrian Hamster Embryo cells transformation assays) on the basis of the published results, seemed to show a considerable sensitivity in predicting carcinogenicity, although they do not show high specificity.

Animals↗
PubMed1985

Cluster analysis of short-term tests: a new methodological approach.

A totally data-based approach to the evaluation of short-term tests is proposed. The performances of 22 tests over a range of 42 chemicals (data from literature) were studied by cluster analysis. The comparison between them was performed only on the basis of their responses to the chemicals. Two different clustering methods produced a coincident classification, pointing to a clear resolution of all tests into 3 groups with common characteristics. With respect to carcinogen discrimination, cluster 1 showed the highest sensitivity and the lowest specificity. Cluster 3 had opposite characteristics. The tests of cluster 2 showed intermediate features. As far as the membership to clusters is concerned, the literature data about the responses to chemicals indicated a strong test system specificity. This apparently overcame both phylogeny and end-point community. A major characteristic of the present approach is the ability to elicit underlying patterns, the knowledge of which can contribute both to hypothesis formulation and be useful for practical purposes.

Animals↗
PubMed1985

Rational approach to the evaluation of short-term tests: analysis of a homogeneous data base.

The major thrust in this study is the analysis by mathematical classification techniques of a homogeneous set of data on short-term tests. The data base generated by the International Program for the Evaluation of Short-Term Tests for Carcinogens was chosen as the model system and was studied first by cluster analysis. For this purpose, an adequate subset of data was selected and the associations between tests were explored on the basis of their performances over a range of chemicals. Then the complementary analysis of the functional relationships between the chemicals, in respect to their genotoxic effects, was performed. In both cases, a clearly structured underlying typology was brought out. Specific indications were suggested by this analysis. First, the data base studied indicated a relative independence of the performances of the assays from phylogeny and genetic endpoints. Second, the chemicals assayed were grouped together (on the basis of functional similarities) according to relationships that may represent a ground for structure-activity relationship investigations. A further important topic of this study was the quantitative evaluation of the test performances in respect to carcinogenicity prediction. To assess the effectiveness with which short-term assays can detect carcinogens and noncarcinogens, discriminant-analysis techniques were applied. On the data set considered here, the short-term tests showed 83.9% global ability to correctly classify chemicals as carcinogens or noncarcinogens. Even if these results are directly dependent on the representativity of the data set chosen, they clearly point out to the high heuristic potency of applying data-analysis techniques to genetic toxicology research.

Animals↗
PubMed1984

Biological monitoring of workers in the rubber industry. II. UV-induced unscheduled DNA synthesis in the lymphocytes of vulcanizers.

DNA-repair ability was estimated in a group of vulcanizers by measuring in vitro UV-induced unscheduled. DNA synthesis (UDS) in peripheral lymphocytes, and compared with that of an adequate control group. A considerable interindividual variability was shown by the UDS responses of the subjects studied both in the control and exposed population. Significantly (P = 0.0158) decreased UDS values were observed among the vulcanizers as compared to the referents. Neither age nor cigarette-smoking was observed to affect the UDS response, thus suggesting an association between the industrial exposure and decrease in the DNA-repair rate.

Cells, Cultured↗
PubMed1983

DNA repair induction by cytostatic drugs in proliferating and quiescent MRC-5 cells.

The repair of DNA damage is closely related to cell cycle, in terms of both modulation of repairing ability throughout the cell cycle and perturbations in replication. We have studied the induction of Unscheduled DNA Synthesis (UDS) in human fibroblasts (MRC-5) by some chemotherapeutic agents, selected for their different mechanisms of action. To take into account the interaction between repair and replication systems, the experiments were performed in both proliferating and quiescent cultures; semiconservative DNA synthesis inhibition was examined by microphotometric measurements in the same autoradiographic preparations used for UDS analysis. Vincristine, methotrexate and 6-thioguanine induced no UDS. Adriamycin, actinomycin D, and, to a lesser extent, cyclophosphamide and thiotepa gave positive results only in proliferating cultures, whereas bleomycin was an effective inducer of UDS in quiescent cells, with weak UDS levels in proliferating ones. In all these cases, the combined analysis of UDS and semiconservative DNA synthesis inhibition proved to be of value in the assessment of interaction between drugs and DNA in proliferating cultures. The results of our experiments emphasize the importance of the cycling conditions in the cellular response to DNA damage.

Antineoplastic Agents↗
PubMed1979

Mutational studies with diquat and paraquat in vitro.

Diquat and paraquat were assayed in the following tests. (1) Ames test in Salmonella typhimurium (strains TA1535, TA1537, TA1538, TA98 and TA100) with and without rat-liver microsomal fractions. (2) Resistance to 8-azaguanine in Salmonella typhimurium (strain hisG46, TA92 and TA1535. (3) Repair test in Salmonella typhimurium (strains TA1538 and TA1978). (4) Gene mutations in Aspergillus nidulans: 8-AG resistance and methionine suppression (meth A1 locus). (5) Lethal recessive damage in Aspergillus nidulans. (6) Unscheduled DNA synthesis (UDS) in human epithelial-like cells (EUE). Diquat and paraquat were positive in S. typhimurium (in the repair test and the 8-AG resistance system), in A. nidulans (for gene mutations and lethal recessive damage induction) and in EUE cells (UDS induction).

Animals↗
PubMed1979

A new in vitro method for testing plant metabolism in mutagenicity studies.

A rapid method was proposed to detect whether a harmless agricultural chemical can be converted into a mutagenic one by plant metabolism. The method is based on the use of Nicotiana alata cell cultures. Results obtained with five pesticides (atrazine, dichlorvos, tetrachlorvinphos, Kelevan, and maleic hydrazide) suggest that the proposed method simulates the metabolism of the whole plant. This procedure was also successfully applied to the genetic system of Aspergillus nidulans. One pesticide, atrazine, induced mutations and somatic segregation only after metabolism during cocultivation with N. alata cells.

Atrazine↗
PubMed1979

Histological lesions in the testis of infertile men with varicocele.

Varicocele frequently causes male infertility and histological lesions at the contralateral testis. The most frequent lesions found in this study included maturation arrest in the spermatidic phase, cellular and acellular thickening of the tubular wall, and degeneration of the Leydig cells. These lesions were typical of varicocele and their simultaneous presence suggests that scrotal temperature and modified endocrine secretion of the interstitial testis play a role in the pathogenesis of this type of infertility.

Humans↗