The effects of iodinated glycerol, trichlorfon, and acetaminophen on tumor progression in a Fischer rat leukemia transplant model.
Sixty-day bioassays of iodinated glycerol, trichlorfon, and acetaminophen were conducted using a leukemia transplant model in 6- to 8-week-old F344 rats to investigate the potential of these chemicals to affect tumor progression. The chemicals were administered in the drinking water at doses that approximated those used in previously conducted 2-year carcinogenesis studies. Simultaneous with dose administration, half of a group of young, healthy, syngeneic rats were given subcutaneous transplants of mononuclear cells derived from spleens of leukemic donors. Variables used to quantitate tumor progression included body weight, spleen weight, white blood cell (WBC) and red blood cell (RBC) counts, packed cell volume, hemoglobin concentration, and platelet counts. Iodinated glycerol at 1.25 or 2.5 mg/ml caused a greater increase in leukocytosis in dosed transplant recipients in comparison to that experienced by undosed recipients: trichlorfon at 2.5 or 5.0 mg/ml enhanced splenomegaly and induced greater reductions in RBC parameters in dosed recipients in comparison to that experienced by undosed recipients. Acetaminophen at 3.0 and 6.0 mg/ml resulted in insignificant but dose-related increases in spleen weight and leukocytosis only in the female rat transplant recipients, as was observed in 2-year studies. Based on results from the short-term leukemia transplant model, data from 2-year carcinogenicity studies, and structure-activity considerations, exposure to iodinated glycerol and trichlorfon was more strongly associated with the expression of leukemia than exposure to acetaminophen. The potential carcinogenicity of each of these chemicals should be taken into consideration when calculating estimates of risk and decisions for their use.
Dieter
M P
MP
National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Maronpot
R R
RR
Jameson
C W
CW
Ward
S M
SM
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D004195:Disease Models, Animal; D005100:Expectorants / Q000633:toxicity*; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives* / Q000633:toxicity; D007942:Leukemia, Experimental / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D014236:Trichlorfon / Q000633:toxicity*
D005100:Expectorants; D000082:Acetaminophen; C015372:iodinated glycerol; D014236:Trichlorfon; D005990:Glycerol