Inositol and inositol hexaphosphate suppress cell proliferation and tumor formation in CD-1 mice.
In previous studies, we have shown that inositol hexaphosphate (InsP6), a constituent of cereal diet, inhibited azoxymethane-induced experimental large intestinal cancer (LIC) in Fischer 344 rats. We now report a similar antineoplastic action of InsP6 in CD-1 mice injected with 1,2-dimethylhydrazine (DMH). We had hypothesized that InsP6 may bring about this effect by undergoing dephosphorylation to lower phosphorylated forms; the ready availability of Ins, to react with phosphates, may increase the total amount of the lower phosphorylated Ins and potentiate the action of InsP6. LIC induced by DMH (15 mg/kg/week x 13) in mice given a mixture of 1% InsP6 + 1% Ins show a significant reduction (P less than 0.005) in LIC prevalence over InsP6 treatment. Surprisingly, Ins, an in vitro growth promoting agent also caused a significant (P less than 0.001) suppression of LIC. InsP6 +/- Ins also showed a concomitant reduction in the mitotic rate in the non-neoplastic epithelium. Body weight data did not suggest any overt toxic effect of long-term administration of InsP6, Ins or InsP6 + Ins. Since InsP6 is antineoplastic in two species of experimental animals, it should, in combination with Ins, be considered in our strategies for prevention of large intestinal cancer.
Shamsuddin
A M
AM
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
Ullah
A
A
Chakravarthy
A K
AK
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004127:Dimethylhydrazines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007294:Inositol / Q000494:pharmacology*; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007420:Intestine, Large / Q000187:drug effects / Q000473:pathology; D008297:Male; D008763:Methylhydrazines / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D010833:Phytic Acid / Q000494:pharmacology*; D012016:Reference Values
D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D007294:Inositol; D010833:Phytic Acid; D019813:1,2-Dimethylhydrazine