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Effect of dietary zinc intake on mammary tumorigenesis induced by N-methyl-N-nitrosourea in rats

University of British Columbia

The overall objective of this study was to investigate the effect of dietary zinc intake on mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in rats. In Experiment 1, twenty-one-day-old female Sprague-Dawley rats were randomly assigned to: severe-low-zinc (lmg zinc/kg diet, Z l ) , marginal-low-zinc (3mg zinc/kg diet, Z3), control (31mg zinc/kg diet, Z31), high-zinc (171mg zinc/kg diet, Z171), very-high-zinc (346mg zinc/kg diet, Z346), pair-fed-to-severe-low-zinc (PZ31-Z1) and pair-fed-to-marginal-lowzinc (PZ31-Z3) groups. On day one of the experiment, each dietary treatment group was further divided into sham- and MNU-treated (50 mg/kg body weight, i.p.) groups (n = 6). After 100 days, the plasma, liver, kidney, heart, lung, muscle, femur, small intestine, skin, normal mammary gland and mammary tumor were removed for zinc determination. Body zinc distribution as indicated by tissue zinc concentrations was mainly affected by dietary zinc intake, but not MNU treatment. MNU-induced mammary tumorigenesis resulted in an accumulation of zinc in mammary tumors. In Experiment 2, twenty-one-day-old female Sprague-Dawley rats were randomly assigned to: marginal-low-zinc (3mg zinc/kg diet, Z3), required-zinc (12mg zinc/kg diet, Z12), control (3lmg zinc/kg diet, Z31), high-zinc (155mg zinc/kg diet, Z155), pair-fed-with-required-zinc-diet (PZ12) and pair-fed-with-control-diet (PZ31) groups. On day one of the experiment, the rats were injected with MNU (40 mg/kg body weight, i.p.). After 28 and 56 days, mammary gland whole mounts were prepared to detect microscopic lesions («=6). The remaining 24 rats were maintained on the assigned diet for 98 days to assess mammary tumorigenesis. Tissue zinc concentrations were also determined and found to be essentially not affected by MNU-induced mammary tumorigenesis. Tumor incidence in Z3 rats was significantly lower than that in Z12, Z31 and Z155 rats (p<0.05) due, at least in part, to the reduced feed intake associated with zinc deficiency. Tumor incidence in Z3 rats was significantly lower than that in PZ12 rats (p<0.05), but was the same as in PZ31 rats. Dietary zinc intake had no effect on the tumor multiplicity, tumor weight and tumor burden during MNU-induced mammary tumorigenesis Overall, these results suggest that dietary zinc intake is critical in modulating palpable MNU induced mammary tumor formation in rats when feed intake is reduced.

Thesis/Dissertation

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2009-06-29

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http://hdl.handle.net/2429/9812

Agricultural Economics

University of British Columbia

UBCV

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