Effects of cigarette smoke and disulfiram on tumorigenicity and clastogenicity of ethyl carbamate in mice.
Exposure of male Balb/C mice to mainstream cigarette smoke for 4 months, starting 10 or 30 days before the administration of ethyl carbamate (0.3% in drinking water for 3 weeks), resulted in an up to 57.6% (P < 0.05) decrease of lung adenoma multiplicity. However, the number of ethyl carbamate-induced lung tumors was not significantly affected by exposure to cigarette smoke when ethyl carbamate was injected i.p. in single doses of 0.5 or 1.0 g/kg, irrespective of the different treatment schedules used, i.e. (a) 10 days before and 4 days after the ethyl carbamate injection; (b) throughout the experiment starting 10 days before the ethyl carbamate injection, and (c) until the end of the experiment, starting 30 days after the ethyl carbamate injection. Disulfiram (500 mg/kg), given by gavage 24 h and 1 h before the ethyl carbamate injection, decreased by 88.5% (P < 0.001) the multiplicity of lung adenomas but had no effect on tumorigenesis when administered after the carcinogen injection. Proadifen (SKF-525 A, 50 mg/kg) injected i.p. 24 h and 1 h before and 24 h and 48 h after the injection with ethyl carbamate tended to decrease the multiplicity of lung adenomas, but not to a significant extent. Furthermore, disulfiram given 24 h and 1 h before the i.p. administration of ethyl carbamate completely prevented its clastogenicity in mouse bone marrow. On the other hand, cigarette smoke, which was per se a weak clastogen in bone marrow erythroblasts, synergistically potentiated the clastogenic response to ethyl carbamate in a more than additive fashion.
Balansky
R M
RM
National Centre of Oncology, Sofia, Bulgaria.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004221:Disulfiram / Q000494:pharmacology*; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced / Q000209:etiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014520:Urethane / Q000008:administration & dosage; D014881:Water Supply
D012906:Smoke; D014520:Urethane; D003577:Cytochrome P-450 Enzyme System; D004221:Disulfiram