Use of the Central Mudminnow (Umbra limi) in the Development and Evaluation of a Sister Chromatid Exchange Test for Detecting Mutagens in Vivo

Abstract

Genetic toxicology is an area of scientific research which is receiving increasing attention. The increasing number of regulations regarding environmental mutagens and carcinogens has stimulated the development of numerous short-term screening test systems capable of detecting these substances. The sister chromatid exchange (SCE) test has become a popular test method both in vitro and in vivo, particularly because of its high sensitivity and relatively simple methodology. SCEs involve the symmetrical exchange of deoxyribonucleic acid (DNA) segments between homologous chromatids which can be readily visualized in appropriately treated and stained metaphase chromosomes. Though the precise mechanism or mechanisms remain unknown, SCE correlates well with, and may be predictive of, genetic damage. The experiments reported here were designed to evaluate the use of the central mudminnow (Umbra limi) in an in vivo SCE screening test. The mudminnow's karyotype facilitates its use in the SCE test. Four known mutagens were tested: two direct acting—methyl methanesulfonate (MMS), and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)—and two indirect acting—cyclophosphamide (CP) and dimethylnitrosamine (DMN). Intraperitoneal injection of each compound produced a dose-dependent increase over control frequencies of SCEs in intestinal metaphase chromosomes. The sensitivity and efficiency of the mudminnow SCE test were confirmed and the results compared with those from other commonly used mutagenesis assays. Application of these procedures to other aquatic organisms having a broader toxicological data base should facilitate the development of a model aquatic system that is useful for studying the potential for genetic damage along with other acute and chronic effects.