Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics

The term apoptosis is proposed for a hitherto little recognized mechanism of controlled cell deletion, which appears to play a complementary but opposite role to mitosis in the regulation of animal cell populations. Its morphological features suggest that it is an active, inherently programmed phenomenon, and it has been shown that it can be initiated or inhibited by a variety of environmental stimuli, both physiological and pathological

Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha-ras oncogenes and is associated with endonuclease availability.

Oncogenes and oncosuppressors can deregulate cell replication in tumours, and recently have been shown to influence the probability of apoptosis. The effects of human c-myc and mutated (T24) Ha-ras oncogenes on susceptibility to apoptosis were investigated by introducing them into immortalised rat fibroblasts. The resulting family of transfectants showed closely similar measures of proliferation, but widely divergent rates of apoptosis, differing by up to fifteen-fold, that correlated inversely with population expansion rates in vitro. T24-ras transfectants with moderate or high p21ras expression showed reduced apoptosis, and this was reversed by pharmacological inhibition of membrane localisation of p21ras by mevinolin. In contrast, c-myc stimulated apoptosis, and this was further enhanced by serum deprivation. Inducibility of effector proteins represents one possible mechanism of genetic control of the susceptibility to apoptosis, and its investigation showed that c-myc was associated with expression by viable cells of latent calcium/magnesium sensitive endonuclease activity characteristic of apoptosis. In contrast, endonuclease activity was not detected in viable cells of a T24-ras transfectant expressing high levels of p21ras. Thus, there appeared to be differential regulation of susceptibility to apoptosis, positively by c-myc and negatively by activated ras, and this was associated with availability of endonuclease activity. Genetic modulation of apoptosis in human neoplasms is likely to influence net growth rate, retention of cells acquiring new mutations and response to certain chemotherapeutic agents

Human papillomavirus type 18 is associated with less apoptosis in fibroblast tumours than human papillomavirus type 16.

In human cervical neoplasia human papillomavirus (HPV) type 18 has a higher cancer/cervical intraepithelial neoplasia (CIN) prevalence ratio than HPV 16. Fibrosarcomas derived from rat fibroblasts transfected with HPV 16 or 18 genomes showed increased apoptosis compared with controls. However, HPV 18 was associated with significantly less apoptosis than HPV 16, affording one possible explanation for the more rapidly progressive cervical neoplasia associated with HPV 18

A model for the generic alpha relaxation of viscous liquids

Dielectric measurements on molecular liquids just above the glass transition indicate that alpha relaxation is characterized by a generic high-frequency loss varying as $\omega^{-1/2}$, whereas deviations from this come from one or more low-lying beta processes [Olsen et al, Phys. Rev. Lett. {\bf 86} (2001) 1271]. Assuming that long-wavelength fluctuations dominate the dynamics, a model for the dielectric alpha relaxation based on the simplest coupling between the density and dipole density fields is proposed here. The model, which is solved in second order perturbation theory in the Gaussian approximation, reproduces the generic features of alpha relaxation