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Incubation of Ehrlich ascites tumor cells in their own ascites fluid induced a reversible metabolic adaptation to these "starvation" conditions which was associated with a fragmentation of DNA. Endogenous poly(ADP-ribose) residues also increased, reaching within 1-3 h values 6-10 times higher than in cells taken directly from the mouse peritoneum. The NAD content changed only slightly while dimethyl sulfate-induced accumulation of poly(ADP-ribose) (10-fold within 30 min) was associated with a rapid depletion of NAD (85% lost at 30 min). Nevertheless, turnover of poly(ADP-ribose) as measured by the decay rate of the polymer upon addition of benzamide was dramatically stimulated in both situations, reaching apparently identical half-lives (t 1/2 approximately equal to 1 min) in "starved" and in alkylated cells. However, since penetration of benzamide into the nucleus may be the rate-limiting factor in these studies, turnover of poly(ADP-ribose) in dimethyl sulfate-treated cells may still be much higher than that in "starved" cells. In cells treated with dimethyl sulfate, suppression of poly(ADP-ribose) synthesis by benzamide did not interfere with DNA fragmentation or with DNA resealing as determined by the nucleoid procedure. By contrast, starvation induced a type of DNA incision that was prevented by benzamide. It is proposed that starvation-induced scission of DNA occurs at specific ("regulatory?") sites requiring poly(ADP-ribose) formation to take place, while fragmentation of DNA at random as seen with alkylating agents is associated with, but not dependent on, increased poly(ADP-ribosyl)ation.

The one feature that permits us to consider disorders as biologically diverse as diabetes, asthma, epilepsy, and hemophilia in the same light is the simple fact of their chronicity. Because most chronic illnesses are not curable and few will improve spontaneously, the care of children with these disorders is frustrating and complex. For many of these children the assistance of co-professionals is required, and the pediatrician's job becomes as much that of manager as active therapist. Because these disorders will persist for long periods if not indefinitely, there is a distinct risk that some children will begin to regard themselves as "sick" and "defective," rather than as persons with a sickness or defect. The evidence suggests, when this occurs, that secondary psychological and social disabilities follow, so that eventually the original disability may be compounded by secondary handicaps that will have further adverse effects on the child's future.1 The