The effect of N-nitrosodimethylamine and N-nitroso-N-benzylmethylamine on [3H]thymidine incorporation into the DNA of target and non-target tissues in the zinc-deficient rat.
The influence of dimethylnitrosamine (NDMA), a liver carcinogen and nitrosobenzylmethylamine (NBMA) as esophageal carcinogen on [3H]thymidine incorporation into DNA was studied in the esophagus, liver, forestomach and gastric-stomach of fasted zinc-deficient and pair-fed zinc-sufficient rats, measured 1 h after the thymidine injection. In the untreated animals, dietary zinc deficiency significantly depressed [3H]thymidine incorporation (89%) into the DNA of forestomach only. NDMA, administered 4 h before death at 30 mg/kg, produced 50-55% inhibition in [3H]thymidine incorporation in the esophagus of rats of both dietary groups. This inhibition became more pronounced in the forestomach, reaching 90-94% in the zinc-deficient forestomach and 63-86% in their zinc-sufficient counterparts at NDMA levels ranging from 5 to 20 mg/kg. NBMA at 2 mg/kg produced 60% inhibition in the DNA synthesis of zinc-deficient esophagus and 40% in the corresponding zinc-sufficient ones, this difference being significant at P less than 0.01. On the other hand, [3H]thymidine incorporation in the forestomach DNA was markedly lowered in the presence of NBMA. Recovery of DNA synthesis in the 4 tissues from a single dose of NDMA or NBMA was monitored up to 12 days. Following NDMA injection, [3H]thymidine incorporation in the forestomach of both dietary groups remained inhibited (3% of untreated control) for 5 days, a significant recovery (45% of untreated control) was observed only in the zinc-sufficient animals. Following NBMA injection, [3H]thymidine incorporation was also inhibited in the zinc-deficient esophagus for a longer time than in the zinc-sufficient ones. In autoradiographic studies, the percentage of cells showing 30 or more grains/nucleus was significantly decreased (P less than 0.001) in the NBMA-treated and marginally decreased (P less than 0.05) in the NDMA- or NBMA-treated zinc-deficient and zinc-sufficient rats as compared with the saline-treated zinc-sufficient controls. These results were discussed in the light of our previous findings that NBMA enhanced esophageal tumorigenesis in the zinc-deficient rats and that NDMA, a liver carcinogen produced forestomach tumors in the zinc-deficient but not in the zinc-sufficient rats.
D000818:Animals; D004247:DNA / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D015032:Zinc / Q000172:deficiency*
D004247:DNA; C014707:nitrosobenzylmethylamine; D015032:Zinc; D004128:Dimethylnitrosamine; D013936:Thymidine