| Toxicity | A naturally occurring
alkylating agent that is produced by the cycad. It was found
originally as the active agent formed from cycasin (methylazoxymethanol-
β-D-glucoside). Ingestion of this plant by animals
or humans has been associated with hepatotoxicity, carcinogenicity,
and teratogenesis. MAM is an alkylating agent that is
probably metabolized to diazomethane, that subsequently forms
active methyl groups that methylate nucleotide bases and
impair DNA and RNA synthesis. Administration of MAM during
fetal life causes a microcephaly that is associated with
extensive necrosis in the area normally occupied by differentiating
cells and seems to result from the disruption of cell replication.
Administration restricted to postnatal life has selective
effects on areas that mature postnatally. Marked cerebellar
lesions characterize the neuropathology observed following
postnatal administration to experimental animals, with measurable
but less dramatic effects on the hippocampus and olfactory
bulb, two regions that undergo a significant part of their development
postnatally. Behaviorally, the animals show fairly specific
neurological signs related to disruption of motor function.
Anatomical findings are characterized by decreased cerebellar
mass, diminished numbers of cells that can be attributed to a
deficit in the number of granule cells. In contrast, postnatal
MAM effects on developing spinal cord are characterized by
fairly specific decreases in indices of glia and myelin formation,
again consistent with the mainly prenatal differentiation of
this region, that is therefore spared. |
