Onset of apoptotic DNA fragmentation can precede cell elimination by days in the small intestinal villus.
DNA fragmentation is a hallmark of apoptosis, and has been viewed as a short-lived process (<hour) that immediately precedes cell elimination. However, use of sensitive techniques like in situ end-labelling plus (ISEL+) has indicated that the period between the initiation of detectable fragmentation and cell elimination could be longer (days). To address this possibility, we used a model system of cell death and replacement, the murine small intestinal villus. Pulses of 5-bromo-2'-deoxyuridine were used to follow quantitatively cohorts of cells from their generation in the crypts to their elimination at the villus tips, resulting in a temporal 'yard-stick' where position on the villus indicated time before cell elimination; these data allowed a mathematical description of cell movement and clearance. Combining these data with ISEL+ quantitation, enterocytes were found to commence and maintain DNA fragmentation 2 - 3 days before elimination, a phenomenon that likely has relevance to studies on apoptosis also in other systems.
Pompeiano
M
M
Department of Pharmacology, School of Medicine, University of California, San Diego, California, USA.
Hvala
M
M
Chun
J
J
D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine; D002465:Cell Movement; D016922:Cellular Senescence; D053938:DNA Fragmentation; D007421:Intestine, Small / Q000166:cytology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D001973:Bromodeoxyuridine