Zinc deprivation promotes progression of 1,2-dimethylhydrazine-induced colon tumors but reduces malignant invasion in mice.
The aim of this study was to characterize colon tumor development and invasiveness associated with dietary zinc deprivation. Colon carcinogenesis was initiated by eight weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH) at 12 mg DMH base/kg body wt in groups of mice maintained on diets containing 30 micrograms/kg dietary zinc (zinc adequate, ZA) or 3 micrograms/kg dietary zinc (zinc deprived, ZD). All mice were killed 24 weeks after the last injection of DMH. Mean zinc concentration in the liver was significantly lower in the ZD group than in the ZA group. The total number of grossly detectable colon tumors was the same in both dietary groups. However, histopathological study of each tumor revealed significantly more adenomatous polyps (AP) and invasive adenocarcinomas (CA) in the ZA group, whereas the ZD group had significantly more noninvasive carcinomas in situ (CIS). It appears that zinc deprivation stimulated progression of AP to noninvasive CIS but retarded the progression of noninvasive CIS to invasive CA. Immunohistochemistry of tumors from ZA and ZD mice indicated increased amounts of type IV collagenase in epithelial tumor cells and in stromal cells adjacent to tumor tissue regardless of the amount of dietary zinc consumed. It is suggested that zinc deprivation may limit function of zinc-requiring enzymes such as superoxide dismutase and type IV collagenase, resulting in enhanced progression of AP to noninvasive CIS and retardation of invasion of CIS to become CA, respectively.
Carter
J W
JW
Department of Public Health Sciences, Wichita State University, KS 67260-0043, USA.
Lancaster
H
H
Hardman
W E
WE
Cameron
I L
IL
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002273:Carcinogens; D002278:Carcinoma in Situ / Q000139:chemically induced / Q000473:pathology; D017364:Collagenases / Q000032:analysis / Q000378:metabolism; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology*; D004032:Diet; D004127:Dimethylhydrazines; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D020780:Matrix Metalloproteinase 9; D051379:Mice; D009361:Neoplasm Invasiveness; D009929:Organ Size; D015032:Zinc / Q000008:administration & dosage* / Q000032:analysis / Q000172:deficiency*
D002273:Carcinogens; D004127:Dimethylhydrazines; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D019813:1,2-Dimethylhydrazine; D015032:Zinc