Carcinogenesis, Vol 19, 2043-2047, Copyright © 1998 by Oxford University Press
DC Wolf, TL Goldsworthy, EM Donner, R Harden, B Fitzpatrick and JI Everitt
Hormonal influences are known to affect the development of renal cell
carcinoma in man and laboratory animal models. We tested the hypothesis
that estrogen treatment or ovariectomy of rats modulates renal tumor
development using tuberous sclerosis 2 (Tsc2) heterozygous mutant (Eker)
rats in which a germline mutation predisposes the animals to renal cell
tumor development. Two-month-old female wild-type and Eker rats were
ovariectomized or sham-operated and treated with placebo or 5 mg
17beta-estradiol in s.c. pellets for 6 or 10 months. Rats were examined at
8 or 12 months of age, at which time the numbers of renal tumors and
preneoplastic foci were quantitated and the severity of nephropathy was
assessed. In contrast to what may have been expected, prolonged estrogen
treatment enhanced the development of hereditary renal cell tumors, with a
2-fold greater number of preneoplastic and neoplastic renal lesions
compared with untreated Eker rats. Ovariectomized Eker rats had 33% fewer
renal lesions than the unmanipulated control group. No tumors or
preneoplastic lesions were present in wild-type rats at either time point.
Estrogen treatment increased the severity of nephropathy in both wild-type
and Eker rats, whereas ovariectomy was protective against nephropathic
changes. Although estrogen is not a rat renal carcinogen, it enhanced the
development of hereditary renal cell tumors when administered to Eker rats.
Eker rats heterozygous for a mutation in the Tsc2 locus provide a good
model in which to study how genetic and hormonal factors contribute to the
development of renal cell tumors and to understand the influence genetic
susceptibility has on the development of renal cell carcinoma.
ARTICLES
Estrogen treatment enhances hereditary renal tumor development in Eker rats
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
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