Synthesis report of the step project detection of germ cell mutagens

被引:17
作者
Adler, ID
Anderson, D
Benigni, R
Ehling, UH
Laehdetie, J
Pacchierotti, F
Russo, A
Tates, AD
机构
[1] BRITISH IND BIOL RES ASSOC, DEPT GENET & DEV TOXICOL, CARSHALTON SM5 4DS, SURREY, ENGLAND
[2] IST SUPER SANITA, COMPARAT TOXICOL & ECOTOXICOL LAB, I-00161 ROME, ITALY
[3] TURKU UNIV, INST BIOMED, DEPT MED GENET, FIN-20520 TURKU, FINLAND
[4] ENEA CASACCIA, SECT BIOL & TOXICOL, I-00060 ROME, ITALY
[5] UNIV PADUA, DEPT BIOL, I-35121 PADUA, ITALY
[6] LEIDEN STATE UNIV, MGC, DEPT RADIAT GENET & CHEM MUTAGENESIS, NL-2333 AL LEIDEN, NETHERLANDS
关键词
germ cell mutagen; genetic risk;
D O I
10.1016/0027-5107(95)00240-5
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The project 'Detection of Germ Cell Mutagens' was designed with three major goals: (1) Detection and characterization of germ-cell mutagens; (2) standardization and validation of new germ-cell tests; and (3) development of a data base on germ-cell mutagenicity. All three goals were achieved, The classical germ-cell tests were applied to characterize the genetic effects of acrylamide (AA), 1,3-butadiene (ED), trophosphamide (TP) and urethane (UR), All but UR were found to cause heritable genetic damage. The experimental data obtained for AA and ED were the basis for genetic risk evaluations during the EC/US Workshop on Risk Assessment 'Human Genetic Risk from Exposure to Chemicals, Focusing on the Feasibility of the Parallelogram Approach'. Nine chemicals were employed to validate the spermatid micronucleus assay with mice and rats: AA, ED and its metabolites 1,2-epoxybutene-3 and 1,2:3,4-diepoxybutane, chlorambucil, mitomycin C, methylnitrosourea, TP and UR. The spermatid micronucleus test was combined with micronucleus tests in somatic cells such as bone marrow or peripheral blood erythrocytes, and splenocytes which allowed a comparison of effects in somatic and germinal cells, Improvements of the spermatid micronucleus test included BrdU-labelling of premeiotic S-phase for the determination of stage sensitivity and fluorescence in situ hybridization with pancentromeric DNA-probes to distinguish between clastogenic and aneugenic events. The results indicate that the spermatid micronucleus test with its improvements is an adequate procedure to detect germ-cell clastogenicity and to compare the activity of chemicals in different tissues and between species, i.e., rats and mice, Other germ cell methods under study were the flow cytometric measurement of testicular sperm DNA and the cytogenetic analysis of preimplantation embryos for chromosomal aberrations and micronuclei. The collection of a reliable germ-cell data base was accomplished through a critical evaluation of the literature and with the data obtained in the present project. Remarkable concordance between responses of germ cell tests to chemical mutagens was the most striking conclusion to be drawn from the present data base.
引用
收藏
页码:65 / 84
页数:20
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