The enhancing role of vitamin A deficiency on chemically induced nephroblastoma in rats.
OBJECTIVE
Vitamin A plays an important role in the prevention of neoplasia. The occurrence of nephroblastoma, a common renal malignancy of childhood, is said to be closely correlated with retardation of differentiation of metanephric blastema. The aim of this study was to clarify the effect of vitamin A deficiency (VAD) in experimental nephroblastoma.


METHODS
Sixty weaning outbred female Wistar rats weighing 40 to 50 g were injected with 0.35% dimethylhydrazine dihydrochloride (DMH) subcutaneously and divided into 2 groups. Animals were fed with diets containing vitamin A, normal diet (ND group; n = 30), and vitamin A-deficient diet (VAD group; n = 30). Serum concentrations of vitamin A on day 120 after DMH injection were assayed. The incidence of nephroblastomas in 2 groups was recorded. The renal tissues were prepared for morphological studies and WT1 messenger RNA (mRNA) detection on day 365 after DMH injection.


RESULTS
The average serum concentrations of vitamin A in the ND group (2.60 +/- 0.53 mumol/L) were significantly higher than that in the VAD group (0.51 +/- 0.26 mumol/L, P < .05) 120 days after DMH injection. On day 365, the incidence of renal tumors in the VAD group (36.7%) was significantly higher than that of the ND group (13.3%, P < .05). Certain histological and ultrastructural features and WT1 mRNA expression patterns observed in these tumors showed that they had a resemblance to human nephroblastomas. Nephrogenic rests (NRs) could be seen in the adjacent normal renal parenchyma. The incidence of NRs in the VAD group (16.7%) was significantly higher than that in the ND group (3.3%, P < .05). The mutant WT1 mRNA expression levels in the VAD group (0.75 +/- 0.11) were significantly higher than those in the ND group (0.24 +/- 0.06, P < .05).


CONCLUSIONS
Vitamin A deficiency can increase development of nephroblastomas in rats, probably via a mechanism of elevated NR remnants and WT1 expression.
Li
Kai
K
Department of Surgery, Children's Hospital, Medical Center of Fudan University (Former Shanghai Medical University), Shanghai 200032, PR China.
Gao
Jiechun
J
Xiao
Xianmin
X
Chen
Lian
L
Zhang
Liang
L
D000818:Animals; D004032:Diet; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000503:physiopathology*; D009154:Mutation; D051381:Rats; D017208:Rats, Wistar; D014801:Vitamin A / Q000097:blood; D014802:Vitamin A Deficiency / Q000150:complications*; D025721:WT1 Proteins / Q000235:genetics / Q000502:physiology; D009396:Wilms Tumor / Q000139:chemically induced* / Q000503:physiopathology*
D025721:WT1 Proteins; D014801:Vitamin A