Enhancement of methylbenzylnitrosamine-induced esophageal carcinogenesis in zinc-deficient rats: effects on incorporation of [3H]thymidine into DNA of esophageal epithelium and liver.
[3H]Thymidine incorporation was measured in esophageal epithelium and liver DNA of rats fed a control diet ad libitum, a zinc-deficient diet or a control diet, pair fed to the food intake of zinc-deficient rats. Additional groups of rats on each diet were dosed i.g. (2.5 mg/kg body wt) one or six times with the esophageal carcinogen methylbenzylnitrosamine (MBN). The zinc-deficient diet significantly increased [3H]thymidine incorporation into esophageal epithelium DNA at 14 days and reached a maximum at 28 days which was approximately three times that of the control ad libitum diet rats. Pair feeding significantly decreased incorporation into the esophageal epithelium DNA relative to the control ad libitum diet, by approximately 60% after 14 days. None of the diets affected [3H]thymidine incorporation in liver DNA. [3H]Thymidine incorporation was significantly inhibited for 48-72 h in the esophageal epithelium and liver DNA of all dietary groups after a single i.g. dose of MBN before returning to predosing levels. The period of inhibition of [3H]thymidine incorporation was lengthened in all groups after six doses of MBN; the greatest increase (10 days) being noted in the esophageal epithelium DNA of the zinc-deficient rats. This inhibition was followed by a significant increase above predosing levels in the esophageal epithelium but not in the liver. The maximum increase occurred 7 days after the completion of MBN dosing in the control ad libitum group, at 14 days in the control pair-fed group and at 36 days in the zinc-deficient group. These findings suggest that the enhancement of MBN-induced esophageal tumors by zinc deficiency is due in part to the increased proliferation of the target cells with a concomitant greater accessibility of the cellular DNA to the carcinogen.
D000818:Animals; D002455:Cell Division; D003043:Cocarcinogenesis; D004247:DNA / Q000378:metabolism*; D004032:Diet; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008938:Mitosis; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism*; D013997:Time Factors; D015032:Zinc / Q000172:deficiency*
D004247:DNA; C014707:nitrosobenzylmethylamine; D015032:Zinc; D004128:Dimethylnitrosamine; D013936:Thymidine