title: Relationship between acute and chronic exposures in mutagenicity studies in mice.
abstract: The relationship between acute and chronic exposures in mutagenicity studies on mammals still lacks experimental data that might permit the decision whether or not the long-term exposures are of significance mutagenicity testing. Fractional application of TEPA, THIOTEPA, EMS, cyclophosphamide and sodium arsenite was made in experiments with mice, by using the dominant-lethal test and cytogenetic analysis of bone marrow. In most experiments the repeated application yielded the same or higher genetic injury than the same total dose at a single application. Negative results are discussed in relation to the threshold dose and the different sensitivity of the germ-cell stage. Possible interaction of mutagens was also studied by analysing the combined effect of a long-term exposure to sodium arsenite, which probably affected the repair mechanism, and of a single dose of TEPA. It is concluded that the present stage of knowledge requires acceptance of the opinion that the genetic risk induced by chronic exposure to a chemical is as serious as that induced by acute exposure.
mesh_terms: D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D001853:Bone Marrow / Q000648:ultrastructure; D001854:Bone Marrow Cells; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005799:Genes, Dominant; D005804:Genes, Lethal; D005821:Genetic Techniques; D007620:Karyometry / Q000379:methods; D051379:Mice; D009153:Mutagens / Q000008:administration & dosage; D013852:Thiotepa / Q000494:pharmacology; D013997:Time Factors; D013721:Triethylenephosphoramide / Q000494:pharmacology
chemical_list: D009153:Mutagens; D003520:Cyclophosphamide; D013852:Thiotepa; D005020:Ethyl Methanesulfonate; D013721:Triethylenephosphoramide; D001151:Arsenic