Figure 4.

Obatoclax induces dramatic ultrastructural vacuolation in H1975 NSCLC cells. (a) H1975-untreated control cells. Untreated cells were processed by the standard protocol adopted for all other samples. The cytoplasm appears normal and is typified by the presence of numerous mitochondria (arrows), cisternae of endoplasmic reticulum (^*) and an extensive array of superficial lamellae (L). The nucleus exhibits scattered arrays of condensed heterochromatin, frequent nuclear pores and a prominent nucleolus. (b) Following 48 h treatment with 500 nM, obatoclax seems to induce a profound vesiculation of the cytoplasm. Many of these membrane vesicles are devoid of obvious content, although a few exhibit some electron dense material within their lumina (arrows). At this stage the nuclei do not appear to have suffered any change. (c) Higher magnification of peripheral cytoplasm reveals that vesicle content is of mixed origin comprising phagocytosed organelles, free ribosomes and endoplasmic reticulum. (d and e) Mitochondria form part of the autophagocytosed pay-load within vesicles, although none have been found to undergo any significant change to their inner membranes