Studies on Methylazoxymethanol, the Aglycone of Cycasin: Methylation of Nucleic Acids in vitro

Schizophrenia-Like Phenotype Inherited by the F2 Generation of a Gestational Disruption Model of Schizophrenia

“…However, given that MAM is a potent alkylating agent (Matsumoto and Higa, 1966), we examined the effect of GD17 MAM administration on the epigenetic regulation of DNA promoters throughout the vHipp using microarray. Interestingly, MAM administration resulted in specific and bidirectional alterations in DNA methylation throughout a relatively small number of promoters (o1% of the probes analyzed).…”

“…However, the exact mechanisms by which MAM induces a schizophrenia-like phenotype are still unknown. MAM is a mitotoxin that selectively affects the developing central nervous system by interfering with mitosis and DNA methylation (Cattabeni and Di Luca, 1997;Matsumoto and Higa, 1966). Given the lack of significant cell loss observed in this model (Moore et al, 2006), it is likely that the effects of MAM may be secondary to aberrant DNA methylation.…”

Contributions of Early Versus Later-Generated Cortical Layers to the Development of Laminar Patterns in Ferret Somatosensory Cortex

“…It was later discovered that the seeds have toxic neurological effects when not properly prepared before ingestion. Since then, studies determined that MAM prohibits synthesis of DNA in dividing cells by methylating the 7 prime position of guanine in DNA and RNA forming 7-methylguanine (Matsumoto, 1966). The methylation of DNA and RNA inhibits the action of DNA and RNA polymerases resulting in decreased nucleic acid synthesis (Zedeck at al., 1970).…”

“…To test the role of early generated layers on subsequent events the development of the subplate and/or deeper cortical layers was disrupted by in utero injection of methylazoxyrnethanol acetate (MAM) into pregnant ferrets on appropriate gestational days. As reported in Chapters 2 and 3, MAM is a toxin that prevents cells from dividing for a short period of time, thereby effectively preventing the birth of a given population of cells that would normally divide at the time of the injection (Matsumoto and Higa, 1966;Matsumoto et al, 1972;Zedeck et at, 1970;Cattabeni and Oi Luca, 1997). Using this method can therefore interfere with the formation of a specific layer of neocortex (Johnston et al, 1981;Jones et aI., 1982;Virgin et al, 1988;Fasolo et aI., 1992).…”

Appendix I. Structural analysis as a means of predicting carcinogenic potential

“…If it is assumed that ac-hydroxylation is a primary step in the activation of all nitrosamines it should follow that analogues having partially or fully blocked os-positions will be non-carcinogenic, and this is broadly observed. Diphenylnitrosamine is noncarcinogenic in several species (Hashida et al, 1973;Innes et al, 1969), t-butyl ethylnitrosamine (63) is both non-carcinogenic (Druckrey et al, 1963) and nonmutagenic (Pasternak, 1963) and the piperidine derivative (64) is of very low or zero carcinogenicity (Lijinsky and Taylor, 1975) (Buglass et al, 1974;Welzel, 1971) and in some (Johnston et al, 1975) Druckrey, 1975;Ward and Weisburger, 1975), and several derivatives are employed as antitumour agents (Wheeler, 1975;Reed and May, 1975 (70) suggested that the carcinogenicity of both cycasin and dimethylnitrosamine may be expressed via a common alkylating intermediate Matsumoto and Higa, 1966), and this has been made more likely by the synthesis of the dimethylnitrosamine intermediate (62), which happens to be isomeric with the cycasin ester (69). Likewise, a similarity between the acute liver toxicity produced by both dimethylnitrosamine and elaiomycin (70) has been noted (Schoental, 1967).…”