INDUCTION OF A WIDE-RANGE OF C-2-12 ALDEHYDES AND C-7-12 ACYLOINS IN THE KIDNEY OF WISTAR RATS AFTER TREATMENT WITH A RENAL CARCINOGEN, FERRIC NITRILOTRIACETATE

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal prox imal tubular necrosis associated with lipid peroxidation and oxidative DNA damage that finally leads to a high incidence of renal cell carci noma in rodents. In the present study, we investigated what kinds of C -2-12 saturated and unsaturated aldehydes and C-7-12 acyloins, metabol ites of saturated aldehydes, are produced in the kidney and liver with in 24 h after single ip administration of 15 mg Fe/kg of Fe-NTA, or af ter repeated (1 or 3 wk) ip administration of 5-10 mg Fe/kg of Fe-NTA. Amounts of twenty one aldehydes and five acyloins were determined by capillary column gas chromatography-negative-ion chemical ionization m ass spectrometry with ammonia as reagent gas. Most of the aldehydes an d all the acyloins measured revealed a significant dose-dependent incr ease 1 to 3 h after single administration in the kidney, among which 4 -hydroxy-2-nonenal (HNE) showed the highest increase (27.3-fold) and m alondialdehyde (MDA) was the most abundant aldehyde (2.40 nmol/100 mg wet tissue). In the liver, however, the increase in aldehydes and acyl oins was less prominent. After repeated administration of Fe-NTA, only 9 aldehydes (ethanal; furfural; trans,trans-2,4-heptadienal; nonanal; trans-2,cis-6-nonadienal; HNE; decanal; trans-4,cis-4-decenal; MDA) a nd 4 acyloins (3-hydroxyheptan-2-one; 3-hydroxyoctan-2-one; 3-hydroxyn onan-2-one; 3-hydroxydodecan-2-one) showed a significant increase. Imm unohistochemistry further demonstrated an increased amount of HNE-modi fied and MDA-modified proteins in the renal proximal tubules after rep eated Fe-NTA administration. Some of the aldehydes measured such as HN E and MDA are reportedly cytotoxic, genotoxic and mutagenic. Accumulat ion of these aldehydes may play a role in this renal carcinogenesis mo del. Copyright (C) 1997 Elsevier Science Inc.