Concurrent analysis of cytogenetic damage in vivo: a multiple endpoint-multiple tissue approach.
Simultaneous assessment of in vivo micronucleus and chromosome aberration endpoints has been described in the rat and the mouse. Bone marrow and spleen cells were utilized for genotoxicity assessment. A cellulose column methodology was used in the micronucleus assay (where applicable) to eliminate nucleated cells and facilitate cytogenetic scoring. The test agents--cyclophosphamide, chlorambucil, and acrylamide--produced qualitatively comparable results between micronucleus and chromosome aberration endpoints and varied slightly on a quantitative basis depending on the type of test agent and tissue studied. The results from test agents such as cyclophosphamide, chlorambucil, acrylamide, dimethylnitrosamine, vincristine, and x-rays indicated that bone marrow cytogenetic results are similar to spleen and that the spleen tissue is at least as sensitive as the bone marrow. The concurrent analysis of cytogenetic damage in vivo using a multiple endpoint-multiple tissue approach described here has the following advantages: a) reducing the overall animal usage, b) clarifying marginal micronucleus and/or chromosome aberration data, c) correlating cytogenetic results from multiple endpoints and multiple tissues, and d) helping the investigation of the mechanism of action of test agents and their potential target organs. Also, the multiple endpoint-multiple tissue approach can be extended to other endpoints, tissues, and species (where appropriate and practical) to obtain detailed genotoxicity information.
Krishna
G
G
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA.
Theiss
J C
JC
D020106:Acrylamide; D000178:Acrylamides / Q000633:toxicity; D000826:Animal Testing Alternatives; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D001854:Bone Marrow Cells; D002273:Carcinogens / Q000633:toxicity*; D002482:Cellulose / Q000737:chemistry; D002699:Chlorambucil / Q000633:toxicity; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000633:toxicity; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D014750:Vincristine / Q000633:toxicity; D014965:X-Rays / Q000009:adverse effects
D000178:Acrylamides; D002273:Carcinogens; D009153:Mutagens; D002699:Chlorambucil; D020106:Acrylamide; D014750:Vincristine; D003520:Cyclophosphamide; D002482:Cellulose; D004128:Dimethylnitrosamine