Carcinogenicity and organ specificity of N-trimethylsilylmethyl-N-nitrosourea (TMS-MNU), N-neopentyl-N-nitrosourea (neoPNU), and N-methyl-N-nitrosourea (MNU) in rats.
The carcinogenicity and organ specificity of TMS-MNU and neoPNU, a carbon-analogue of TMS-MNU, in rats were investigated and compared with those of MNU. Compounds were dissolved in olive oil and rats in the experimental groups received 20 weekly intragastric intubations of 10 mg/kg of MNU or equimolar amounts of TMS-MNU or neoPNU in the same manner. The experiment was terminated when the survivors were sacrificed at the 52nd week after the final administration. In the TMS-MNU and MNU groups, tumors of the forestomach were induced and the incidence was 100% in the groups of both sexes. In addition, tumors of the glandular stomach, nervous system, kidney, and lung were also observed in these groups. Neurogenic tumors were found more frequently in the MNU group than in the TMS-MNU group. The incidence of lung tumors, however, was higher in the TMS-MNU group than in the MNU group. On the other hand, in the control and neoPNU groups, no tumor was found in these organs except the lung, and all tumors observed in these two groups were histologically similar to spontaneous ones in this strain of rats. These results indicate that the carcinogenicity of N-alkyl-N-nitrosoureas is dependent on the chemical structure of their alkyl chain. The result of the present study coincides with the previous result that the species of TMS-MNU in the alkylating step is the same as that of MNU, but different from neoPNU. The difference in the organ specificity between TMS-MNU and MNU demonstrates that the organ specificity is dominantly dependent on the distribution of the chemicals, since TMS-MNU may possibly be distributed differently from MNU because of its different partition property.
Maekawa
A
A
Division of Pathology, National Institute of Hygienic Sciences, Tokyo, Japan.
Onodera
H
H
Kanno
J
J
Furuta
K
K
Nagaoka
T
T
Todate
A
A
Matsushima
Y
Y
Oh-hara
T
T
Kawazoe
Y
Y
D000818:Animals; D002273:Carcinogens; D005260:Female; D008297:Male; D008770:Methylnitrosourea / Q000031:analogs & derivatives* / Q000633:toxicity*; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009607:Nitrosourea Compounds / Q000633:toxicity*; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D012825:Silicon / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014297:Trimethylsilyl Compounds / Q000633:toxicity*
D002273:Carcinogens; D009607:Nitrosourea Compounds; D014297:Trimethylsilyl Compounds; C057695:N-neopentyl-N-nitrosourea; C045827:N-trimethylsilylmethyl-N-nitrosourea; D008770:Methylnitrosourea; D012825:Silicon