Tumor-promoting activity of p-hydroxybenzenediazonium is accelerated in Mg-deficient rats.
Tumor-promoting activity caused by the short-term administration of p-hydroxybenzenediazonium (PDQ) has been assayed in rats fed on a Mg-deficient diet as a reference model versus rats fed on a standard diet as controls. For 5 weeks groups of 20 rats, fed either on the Mg-deficient or standard diet, were treated simultaneously with PDQ. A group of 10 Mg-deficient rats remained untreated. Topical application of PDQ was followed by the appearance of macroscopic alterations in the skin, which were more evident in the Mg-deficient rats. No deaths occurred during the treatment. After 5 weeks' PDQ treatment the rats were killed and histological analyses were made. Tissues from the skin, liver, heart, kidney, lung and thymus were screened by conventional staining methods. Both the PDQ-treated Mg-deficient and PDQ-treated control rats presented tissue lesions, although to a different extent. The untreated Mg-deficient rats showed no such lesions. Mg-deficient rats treated with PDQ developed significant incipient fibrosarcomas (p<0.05) and extended hyperplasia (p<0.001), particularly in the skin, accompanied by a significant increase in the thickness of collagen (mean value: 445.4+/-47.2microm, p<0.05) compared to the control PDQ-treated group (mean values: 258.7+/-36.4microm). The overall results provide objective proof of tumor-promoting activity after 5 weeks' treatment with PDQ. Such a fast response is interpreted as being linked to the increased vulnerability of the membrane caused by Mg deficiency, which would more readily facilitate the toxic activity of p-hydroxybenzenediazonium ions.
Quintero
Bartolome
B
Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain. bqosso@ugr.es
Planells
Elena
E
del Carmen Cabeza
María
M
Esquivias
Javier
J
del Pilar Gutiérrez
María
M
Sánchez
Cristina
C
Aranda
Pilar
P
Zarzuelo
Antonio
A
Llopis
Juan
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003979:Diazonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000097:blood / Q000503:physiopathology*; D008297:Male; D009369:Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013057:Spectrum Analysis
D003979:Diazonium Compounds; C508525:p-hydroxybenzenediazonium