QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP MODELS CORRECTLY PREDICTTHE TOXIC AND ANEUPLOIDIZING PROPERTIES OF 6 HALOGENATED METHANES IN ASPERGILLUS-NIDULANS

In a previous study, the relationships between the chemical structure and the ability of 35 chlorinated aliphatic hydrocarbons to induce ane uploidy and toxicity in Aspergillus nidulans were analyzed. Quantitati ve structure-activity relationships (QSAR) were defined for each of th e biological activities under study: ARR (the dose able to block mitot ic growth), D37 (the dose with 37% of survival) and LEC (the lowest ef ficient concentration in aneuploidy induction). In this study, these Q SAR equations were used to predict the toxic and genetic activity of a further six chemicals, not included in the previous data base: bromot richloromethane, bromoform, bromochloromethane, bromodichloromethane, dibromochloromethane and dibromochlorofluoromethane. Their ARR, D37 an d LEC values were measured, and were in agreement with the predicted v alues, with correlation coefficients around 0.99. Furthermore, the QSA R model, which had previously been developed to discriminate between a neugenic and inactive halogenated hydrocarbons, correctly predicted th e aneugenic activity of five out of six methanes. These correct predic tions confirmed the validity of our QSAR model, according to which the induction of aneuploidy in A. nidulans depends on both the electrophi lic and steric properties of the chemicals, whereas toxicity mainly de pends on steric factors.