Dietary Zinc Modulation of Moloney Sarcoma Virus Oncogenesis¹

To explore the relationship between dietary zinc and the natural history of Moloney sarcoma virus (MSV) oncogenesis, BALB/c mice were fed diets which contained four levels of zinc: 100 ppm zinc (designated control); 9 ppm zinc (designated marginal deficiency); 5 ppm zinc (designated moderate deficiency); and 2.5 ppm zinc (designated severe deficiency). Moreover, because zinc deficiency is associated with some degree of inanition, a group of mice was fed the control diet but in amounts equal to the intake of animals fed 5 ppm zinc. All diets were initiated in 10-week-old mice at 0, 1, 3, and 6 weeks before injection of the MSV. When the diets were introduced simultaneously with the MSV, little significant impact upon natural history of the tumor was observed. With 1 week of prior dietary zinc deprivation, severely deprived mice experienced inhibition of tumor growth. However, with 3 weeks of limited zinc availability prior to MSV injection, alteration of tumor growth was observed and was directly dependent upon the specific level of zinc in the diet. Mice fed 9 and 5 ppm zinc showed an increase in sarcoma growth when compared with control animals while mice fed 2.5 ppm zinc demonstrated a decreased incidence of sarcomas and a reduction in the size of those tumors which developed. Feeding low-zinc diets for 6 weeks resulted in a marked reduction in sarcoma initiation and progression in mice fed 9, 5, and 2.5 ppm zinc. With sufficient severity and duration, animals maintained in low-zinc environments also experienced an increase in tumor latency period and tumor regression time. Caloric restriction, as evidenced by inanition controls, caused markedly altered tumor incidence and kinetics, making it difficult to quantify those effects due to inanition and those due to zinc deficiency. The present experiment underscores the critical influence that magnitude and duration play in determining the ultimate impact of various degrees of zinc deficiency upon tumor initiation and progression and further emphasizes the need for caloric restriction controls in all studies of trace element deprivation.