Anticarcinogenic effects of cadmium in B6C3F1 mouse liver and lung.
The B6C3F1 mouse liver has been widely used for the evaluation of carcinogenic or tumor promoting efficacy of various organic compounds, although little is known about the actions of metallic carcinogens in this system. Thus, the ability of cadmium to initiate or promote tumors in B6C3F1 mouse liver was studied. In promotion studies, diethylnitrosamine (DEN; 90 mg/kg, ip) was given as an initiator to 5-week-old mice followed 2 weeks later by 500 or 1000 ppm of cadmium in drinking water for 50 weeks. DEN caused an elevation of liver tumor incidence (13 tumor bearing mice/45 total) over control (1/48) which was prevented by cadmium (DEN + 500 ppm cadmium, 3/42; DEN + 1000 cadmium, 0/47). Cadmium alone did not further reduce the very low spontaneous liver and lung tumor incidence at approximately 1 year of age. DEN-induced lung tumor incidence (15/45) was also reduced by cadmium (DEN + 500 ppm cadmium, 11/42; DEN + 1000 ppm cadmium, 1/47) to control levels (0/48). In initiation studies, cadmium (20 or 22.5 mumol/kg, sc) was given to 5-week-old mice (n = 30-60) 2 weeks before an established promoting regimen of sodium barbital (BB) in drinking water at 500 ppm level was begun. Barbital in drinking water was given continuously for up to 92 weeks. Such cadmium doses caused acute, focal hepatic necrosis. Mice treated with BB and killed at 97 weeks of age showed an elevation of liver tumor multiplicity (7.44 tumors/liver) over control (2.24) that was prevented by cadmium in a dose-related manner (20 mumol/kg cadmium + BB, 3.93; 22.5 mumol/kg cadmium + BB, 1.87). Cadmium alone given by injection also reduced spontaneous liver tumor multiplicity. These results indicate that cadmium inhibits tumor formation in the B6C3F1 mouse liver initiation/promotion system regardless of route of exposure or sequence of administration. The possibility exists that cadmium has a specific toxicity toward previously initiated cells within liver and lung.
Waalkes
M P
MP
Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201.
Diwan
B A
BA
Weghorst
C M
CM
Bare
R M
RM
Ward
J M
JM
Rice
J M
JM
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents; D001462:Barbital / Q000494:pharmacology; D002104:Cadmium / Q000008:administration & dosage / Q000627:therapeutic use*; D019256:Cadmium Chloride; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D008113:Liver Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D000970:Antineoplastic Agents; D002104:Cadmium; D004052:Diethylnitrosamine; D001462:Barbital; D019256:Cadmium Chloride