Planarians as a model system for in vitro teratogenesis studies

Abstract

Free-living flatworms such as planarians are inexpensive to culture, maintain, and use for toxicologic testing in the laboratory. A considerable number of basic studies by ourselves and others indicate that, in simplified miniature, they possess many features of biochemical and physiologic organization similar to higher animals such as mammals. These include a well-developed brain with a varied behavioral repertoire including complex maneuvers of prey capture and learning, with a number of the same neurotransmitters used in mammalian brain. They are sensitive to a variety of the same toxicants. Undifferentiated totipotent stem cells, i.e., "neoblasts," which are capable of mitosis and differentiation into any of the various specialized cell types, permit regeneration of complete planarians from fragments. They also provide new cells to replace those lost in the normal cellular turnover of nonregenerating planarians. Both regeneration of surgical fragments and aberrant remodeling of whole planarians model important features of embyrogenesis and are potentially useful for assaying teratogens. Results are described from studies in which various representative teratogenic toxicants were tested in these two different planarian paradigms. The potential of planarian cephalic regeneration for behavioral teratogenesis investigations is also indicated.

Teratological research using in vitro systems. V. Nonmammalian model systems.

“…The methodology for using the planarians as an assay for teratogens is described by Best and Morita (16). The animals can be kept in a laboratory, and they will reproduce asexually.…”

“…The suggestion is based partly on the fact that although planarians such as Dugesia dorotocephala and D. tigrina are only onefive millionth the mass of an adult human, the ratio of brain to body weight approximates that of a rat (16).…”

“…Best and Morita (16) have advocated the use of the planarian as a screen for compounds with teratogenic potential. Other more general studies of the toxicity of specific compounds have also been made, e.g., studies of aflatoxin by Llewellyn (17).…”

“…The When tested, planarians exhibit both lethality and sublethal responses such as visible lesions and tumors, head resorption, changes in the incidence of fissioning, changes in behavior, and aberrant morphogenesis. A variety ofcompounds have been tested for acute toxicity with planarians, including alkaloids, drugs, metals, pesticides, toxins, petroleum derivatives, ethanol, and complex toxicant mixtures (16). In terms of sensitivity and type of response, the results of the acute toxicity tests showed values that fell within the range of variability of mammalian values, with the exception of arsenate (16).…”

“…A variety ofcompounds have been tested for acute toxicity with planarians, including alkaloids, drugs, metals, pesticides, toxins, petroleum derivatives, ethanol, and complex toxicant mixtures (16). In terms of sensitivity and type of response, the results of the acute toxicity tests showed values that fell within the range of variability of mammalian values, with the exception of arsenate (16). Teratologic responses have been observed in two types of tests: exposure to the compound after surgical dissection of the animal, and exposure of intact animals to see if they develop and respond abnormally.…”