RELATIONSHIP OF HYDROQUINONE-ASSOCIATED RAT RENAL TUMORS WITH SPONTANEOUS CHRONIC PROGRESSIVE NEPHROPATHY

Hydroquinone exposure has been reported by the National Toxicology Pro gram (NTP) to produce renal tubule adenomas and to exacerbate spontane ous chronic progressive nephropathy (CPN) in male F344 rats. A mechani sm for hydroquinone-related tumorigenesis has not been established, bu t CPN is known to involve, and hydroquinone produces, enhanced renal t ubule cell proliferation. Through an independent review of the renal h istopathology from the NTP study, the grade of CPN and the presence of atypical tubule hyperplasia and adenomas was evaluated. Hydroquinone exposure in males at 50 mg/kg produced a statistically significant inc rease in the grade of CPN. At 0, 25, and 50 mg/kg, 0/44, 4/49, and 15/ 51 male rats had either atypical tubule hyperplasias or adenomas; all were within areas of severe or end-stage CPN and were statistically si gnificantly associated with CPN grade. Additionally, there was a dose- related increase in profiles believed to represent new tubule prolifer ation within areas of advanced CPN, as well as an apparent expansion o f these into unusual complex tubule profiles in end-stage kidneys of t he high-dose male group. In summary, this histopathological review sug gests a mechanism for hydroquinone-related adenoma formation that incl udes enhancement of the severity of CPN coupled with stimulation of tu bule proliferation.