Promotion of hepatocellular foci and adenomas by di(2-ethylhexyl) phthalate and phenobarbital in C3H/HeNCr mice following exposure to N-nitrosodiethylamine at 15 days of age.
Previous studies have shown that phenobarbital (PB), as well as another known liver tumor promoter, alpha-hexachlorocyclohexane (HCH), inhibits hepatic tumor formation in infant N-nitrosodiethylamine (NDEA)-initiated C57BL/6 x C3H/He (B6C3F1) male mice. These inconsistencies in detecting PB and HCH as tumor promoters have raised important questions on the mechanism of tumor promotion in mice, as well as the reliability of the infant B6C3F1 mouse as an initiation model in two-stage carcinogenesis experiments. Therefore, in an effort to avoid the inconsistencies associated with the B6C3F1 mouse, the present study evaluated the ability of two known hepatic liver tumor promoters, di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, and phenobarbital (PB), a barbiturate, to promote hepatocellular tumorigenesis in mice of the C3H/HeNCr strain initiated during infancy. At 15 days of age, male and female C3H/HeNCr mice received either a single ip injection of NDEA (5 micrograms/g body weight) or saline. At weaning (4 weeks of age), mice were divided into 3 groups and treated with either DEHP in the diet (12,000 ppm), PB in the drinking water (500 ppm), or control drinking water and diet for 24 weeks. All mice were killed at 28 weeks of age and the number and size of hepatic foci and adenomas were evaluated. Mice exposed to NDEA+DEHP or NDEA+PB showed significant increases in the number and size of hepatic tumors compared to those receiving NDEA alone. DEHP treatment in males yielded larger adenomas than those seen in PB-treated males.(ABSTRACT TRUNCATED AT 250 WORDS)
Weghorst
C M
CM
Laboratory of Comparative Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201.
Devor
D E
DE
Henneman
J R
JR
Ward
J M
JM
D018248:Adenoma, Liver Cell / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D015994:Incidence; D008113:Liver Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010634:Phenobarbital / Q000633:toxicity*
D004052:Diethylnitrosamine; D004051:Diethylhexyl Phthalate; D010634:Phenobarbital