Influence of 6-mercaptopurine on the prenatal development of the rat cortex.
The prenatal cortex development after the application of 6-Mercaptopurine (6-MP) was studied in the rat embryo. 24 h after application of a single dose of 6-MP on day 12, 13, 14 or 15 of gestation first cell lesions occured in the form of necroses. 48 h after injection of the drug these necroses were most pronounced. Their extent and distribution pattern was, however, dependent on the developmental stage. In the early developmental phase, on days 12 and 13, massive necroses could be observed in the intermediate zone. At later stages of development (drug application on day 14 or 15) damaged cells could occasionally also be found scattered over the whole ventricular wall. The late toxic response to 6-MP treatment suggests that, after incorporation of metabolites of the agent into DNA during the S-phase, at least one additional S-phase is completed before the disturbance created in a cell is sufficient to cause necrosis. The necrosis may be a result of an action of 6-MP directly on DNA or via an affect on transcription. The different extent of the lesion during the various developmental phases suggests different growth dynamics of the cortex.
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology* / Q000473:pathology; D005260:Female; D005865:Gestational Age; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D009336:Necrosis; D051381:Rats
D015122:Mercaptopurine