Neuro-oncogenesis Induced by Nitroso Compounds in Rodents and Strain-Specific Genetic Modifiers of Predisposition

The alkylating substances N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU) are the most potent systemically acting neurocarcinogens in rodents. They induce tumors of the central (CNS) and peripheral nervous system (PNS), which are similar to their human counterparts. The neuro-oncogenic effect of both chemicals depends on the dose, the rodent species, the strain, and the developmental stage at exposure. Neuro-oncogenesis induced by MNU and ENU has been widely used as a model system including studies of molecular mechanisms of malignant transformation, screening of therapeutics, and lately, the genetics of predisposition toward the development of these tumors. The induction of malignant tumors in the PNS of differentially susceptible rat strains made it possible to identify gene loci influencing tumor risk in an allele- and sex-specific way and to gain insight into molecular and cellular mechanisms underlying tumor susceptibility and resistance.