Effects of phlebotomy on the growth of ferric nitrilotriacetate-induced renal cell carcinoma.

The ferric nitrilotriacetate-induced carcinogenesis model is unique in that reactive oxygen species-free radicals are involved in the carcinogenic process. But the effects of iron-withdrawal in the progression of renal cell carcinoma are not well understood. We performed repeated phlebotomies on animals that had been administered ferric nitrilotriacetate in the initiation stage of renal cell carcinoma (phlebotomy group), and compared the development of renal tumors with those not receiving repeated phlebotomies (non-phlebotomy group). Ferric nitrilotriacetate-treated male Wistar rats were randomly divided into 2 groups: a phlebotomy group (21 rats) and a non-phlebotomy group (17 rats). Ten age-adjusted normal rats were also observed as a normal group. Hematocrit was maintained under 25% in the phlebotomy group. Hematocrit levels in the normal group and in the non-phlebotomy group were not significantly different. As a result, the incidence of renal cell carcinoma was not significantly different between phlebotomy and non-phlebotomy animals. However, the total weight of the renal cell carcinoma was significantly heavier in the animals from non-phlebotomy group than in those from the phlebotomy group (23.64 g +/- 18.54 vs. 54.40 g +/- 42.40, P &#60; 0.05). The present study demonstrated that phlebotomy after the administration of ferric nitrilotriacetate did not reduce the incidence of renal cell carcinoma. In addition, we showed that iron withdrawal at the promotion stage of carcinogenesis will retard tumor growth.</p

クエン酸第一ナトリウムと他の汎用薬剤との鉄薬物錯体形成

雑誌掲載版クエン酸第一ナトリウム(SFC)と同時服用後尿色の変化をきたしたとメーカーへ照会があった薬物と,それらと類似構造を持ち尿色の変化をきたす可能性のある薬物を含め,試験管内での色調変化を基準にSFCと他の薬物との相互作用を検討した.色調の変化を示した薬剤の主成分の化学構造式から推定すると,鉄イオンに配位する基は,カルボキシル基,ケト基,ヒドロキシル基,アミノ基などと考えられた.鉄剤による副作用には,消化管で鉄の吸収を障害する可能性と,新たな鉄錯体が生体内で副作用を発現する可能性があげられる.実験の結果,中枢性パーキンソン薬であるbenserazideが,鉄薬物錯体を形成しており,本薬剤と鉄剤との同時服用には注意が必要である.鉄錯体が新たな細胞毒性を発揮する可能性については,鉄錯体の構造,反応性について詳細に検討していないので断定はできないが,文献を渉猟すると無視できないと考えられ