Cellular effects of a brain extract factor or factors inhibiting neuroblastoma cell growth in vitro

The mechanism of inhibition of neuroblastoma cell proliferation in vitro by extract prepared from the brains of newborn mice was partially elucidated. Flow cytometric analysis of propidium iodide-stained cells showed that a significant increase occurred in the pre-G0/G1 cell population after exposure to the extract for 24 hr. Fluorescence microscopy indicated that the pre-G0/G1 cells had small "micronuclei" in association with their nucleus, whereas post-G2/M cells had enlarged propidium iodide-staining nuclei. 3H-thymidine incorporation was unchanged from that of control cells, in cells exposed to the extract for either 6 or 24 hr. No effect was seen on choline acetyl transferase activity or on morphology. These results suggest that the inhibitor blocks neuroblastoma cell proliferation either by inducing an uneven distribution of DNA at the time of cell division or by altering its packaging within the nucleus.