Wainstok de Calmanovici R, Cochón A C, Aldonatti C, Cabral J R, San Martín de Viale L C
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Tumori. 1991 Oct 31;77(5):379-84. doi: 10.1177/030089169107700503.
The present study was undertaken to explore the effect of the presence of hepatic tumors induced by diethylinitrosamine (DENA) on the metabolic heme pathway, and to assess whether these tumors can modify the response of rats to the porphyrinogenic drug hexachlorobenzene (HCB) and whether the above mentioned effects occur to a greater extent in females than males. The results obtained showed that: a) Females were more susceptible to the hepatocarcinogenicity of DENA than males. b) Female normal and DENA treated rats were more susceptible than male rats to the porphyrinogenicity of HCB. c) The presence of hepatic DENA induced tumors could diminish basal hepatic ferrochelatase activity. d) Hepatic tumors could modify the response of animals to a porphyrinogenic drug such as HCB. Thus, both female and male DENA/HBC rats accumulated more porphyrins and showed a lower delta-aminolevulinate synthase and uroporphyrinogen I synthase induction than HCB rats. e) The heme pathway was functional in DENA induced tumors in both male and female rats but they were little affected by HCB.
本研究旨在探讨二乙基亚硝胺(DENA)诱导的肝肿瘤的存在对血红素代谢途径的影响,并评估这些肿瘤是否会改变大鼠对致卟啉药物六氯苯(HCB)的反应,以及上述影响在雌性大鼠中是否比雄性大鼠更明显。所得结果表明:a)雌性比雄性对DENA的肝致癌性更敏感。b)雌性正常和经DENA处理的大鼠比雄性大鼠对HCB的致卟啉性更敏感。c)肝DENA诱导肿瘤的存在可降低肝碱性铁螯合酶活性。d)肝肿瘤可改变动物对致卟啉药物如HCB的反应。因此,雌性和雄性DENA/HBC大鼠比HCB大鼠积累更多的卟啉,且δ-氨基乙酰丙酸合酶和尿卟啉原I合酶的诱导作用更低。e)血红素途径在雄性和雌性大鼠的DENA诱导肿瘤中均起作用,但它们受HCB的影响较小。