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Mycotoxin synergism

Lillehoj, E.B., Ciegler, A.
Microbiology Wash, D C 1975 pp. 344-358
mycotoxins, toxicity, synergism, mycotoxicosis, carcinogens, neoplasms, carcinogenesis, laboratory animals
Mycotoxicologists are particularly conscious of toxic interactions in which the cooperative effect of 2 or more substances elicits a total effect greater than the sum of activities of individual agents; this combined response is called a toxic synergism. Aggregate toxicities in test animals depend on a number of variables, including species, sex, age, nutrition, disease, test procedures, and environmental conditions (temperature, light, and humidity). In aflatoxicosis, young animals are more susceptible than older ones, males more than females, and both ducklings and trout are significantly more sensitive than mice. Within the inherent constraints, several techniques have been developed and adapted to the determination of mycotoxin synergism in test animals. These involve growth rates, organ function, acute toxicity, tissue histology, cellular function, blood chemistry, immunological response, and tumor induction. Particularly useful in measuring mycotoxin synergism is the initiator promoter procedure employed in the mouse skin tumor test. This unique technique provides a 2 step process in which single applications of an initiator substance, e.g. 9,10 dimethyl 1,2 benzanthracene and subsequent treatments with a promoting substance, e.g. croton oil, produce tumors on sensitive mouse strains. Similar dose levels of either initiator or promotor alone are ineffective in causing skin tumors.