Hepatocarcinogenicity of benzo[a]pyrene to rainbow trout by dietary exposure and intraperitoneal injection.
The influence of benzo[a]pyrene [(BP) CAS: 50-32-8] on the induction of certain enzymes within the hepatic mixed-function oxidase (MFO) system and its potential carcinogenicity were examined in rainbow trout (Salmo gairdneri). Nine-week feeding trials were performed with 500 and 1,000 ppm BP to determine trout tolerance to BP. Levels of MFO enzymes, including ethoxyresorufin-O-deethylase (EROD), ethoxycoumarin-O-deethylase (ECOD), benzo[a]pyrene monooxygenase (BPMO), and cytochrome P450 were measured during this time. An 18-month feeding trial of a 1,000-ppm BP dose was initiated in duplicate groups of 100 fingerling rainbow trout. Samples of trout were killed at 6, 12, and 18 months for gross and histologic examination of the internal organs for neoplasms. A group of fifty 10-month-old rainbow trout were given 12 monthly ip injections of 1 mg BP in 0.4 ml propylene glycol (PG), and comparable controls were given PG injections only. The trout were held for an additional 6 months, killed at age 28 months, and examined as in the dietary study. Mean MFO enzyme levels of EROD, ECOD, BPMO, and cytochrome P450 were significantly (P less than .001) elevated, showing dose- and time-response relationships when compared to MFO enzyme levels in control fish. Twelve months after BP exposure was initiated, 15% of the BP-fed fish had histologically confirmed neoplasms of the liver. After 18 months the incidence increased to 25%. No evidence of neoplasia was observed in control fish. BP injected ip resulted in a 50% incidence of hepatocellular neoplasms and in a fibrosarcoma of the liver and papillary adenomas of the swim bladder in 1 fish. These results indicate that BP is a potent inducer of selected hepatic MFO enzymes and establish, for the first time, the hepatocarcinogenicity of BP in an aquatic species.
Hendricks
J D
JD
Meyers
T R
TR
Shelton
D W
DW
Casteel
J L
JL
Bailey
G S
GS
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000473:pathology; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology; D004032:Diet; D004790:Enzyme Induction / Q000187:drug effects; D005354:Fibrosarcoma / Q000139:chemically induced / Q000473:pathology; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008643:Mesentery / Q000187:drug effects / Q000473:pathology; D006899:Mixed Function Oxygenases / Q000032:analysis; D009929:Organ Size / Q000187:drug effects; D010532:Peritoneal Diseases / Q000139:chemically induced; D012487:Salmonidae / Q000378:metabolism*; D014337:Trout / Q000378:metabolism*
D001564:Benzo(a)pyrene; D006899:Mixed Function Oxygenases