SUBTOTAL BUT NOT UNILATERAL NEPHRECTOMY INDUCES HYPERPLASIA AND PROTOONCOGENE EXPRESSION

It is generally accepted that renal compensatory growth after unilater al nephrectomy (Uni) is due to prominent hypertrophy with no involveme nt of protooncogenes. Neither the balance between hypertrophy and hype rplasia nor the expression of the early-growth-related genes has been studied after subtotal nephrectomy (Nx). The occurrence of cystic tubu lar dilatations after Nx may suggest an excessive cell proliferation i n this model. We measured DNA, RNA, and protein content, number of nuc lei per tubular section, as well as c-fos, c-jun, c-myc, c-H-ras, c-si s, and c-erb-B2 protooncogene expression in kidneys taken at time of s urgery and 2, 7, and 14 days after sham operation (control rats), Uni, or Nx. After Uni, hyperplasia was greater than expected (+79% for DNA at day 14) and was associated with moderate hypertrophy (+11% for pro tein/DNA ratio). After Nx, compensatory growth was due only to hyperpl asia(+117% for DNA at day 14), with unchanged protein/DNA ratio (vs. U ni, P < 0.02). The greater hyperplasia after Nx was confirmed by nucle i counting. The protooncogene mRNA expression was constantly absent in control and Uni rats, whereas that of c-fos and c-jun genes was detec ted in Nx rats at day 14 with a 2- to 12-fold increment. The c-fos and c-jun protein levels were also increased at that time in Nx rats. Thi s suggests the following: 1) the cellular events following Uni and Nx are not the same, and 2) the late protooncogene expression in Nx exclu sively could favor a particular type of cell proliferation possibly mo re related with cystic formation than with actual compensatory growth.