Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1988-10-7
pubmed:abstractText
Variation in hepatic metabolism between species may be an important factor in the differences observed in chemical carcinogenesis. We examined 6 chemicals representative of 4 chemical classes in the in vitro hepatocyte DNA repair assay using cells isolated from the Fischer-344 rat, B6C3F1 mouse, Syrian golden hamster, cynomolgus monkey and from human liver. Hepatocytes were isolated by in situ or biopsy liver perfusion and incubated with [3H]-thymidine and the test chemical. Unscheduled DNA synthesis (UDS) was measured as net grains/nucleus (NG) by quantitative autoradiography. Qualitative and quantitative differences in UDS responses were observed for every chemical. Liver cultures isolated from the rat, mouse, hamster, human, and monkey and treated with aflatoxin B1 or dimethylnitrosamine all yielded dose-related increases in NG. Human, rat, and hamster hepatocyte cultures yielded positive responses following exposure to the aromatic amines 2-acetylaminofluorene, 4-aminobiphenyl, and benzidine, whereas cultures isolated from the monkey and mouse yielded less than 0 NG. Treatment with benzo[a]pyrene (BAP) produced strong positive responses in monkey and human hepatocyte cultures, weak positive responses in hamster cultures, and equivocal or negative responses in rat and mouse hepatocyte cultures. Hepatocyte function was assessed by measurement of DNA content, glutathione content, BAP hydroxylase activity, p-nitroanisole-O-demethylase activity, p-nitrophenol conjugation, and urea synthesis rates. The functional capabilities of isolated hamster, monkey, and human hepatocyte cultures do not appear to correlate with UDS responses observed for any compound; however, they indicate that the cultures were metabolically competent at the time of chemical exposure. These studies suggest that rat hepatocytes are a suitable model for human hepatocytes, whereas mouse and male monkey hepatocytes may be insensitive to aromatic amines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
206
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-102
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:3137465-2-Acetylaminofluorene, pubmed-meshheading:3137465-Adult, pubmed-meshheading:3137465-Aflatoxin B1, pubmed-meshheading:3137465-Aflatoxins, pubmed-meshheading:3137465-Aminobiphenyl Compounds, pubmed-meshheading:3137465-Animals, pubmed-meshheading:3137465-Benzo(a)pyrene, pubmed-meshheading:3137465-Biotransformation, pubmed-meshheading:3137465-Carcinogens, pubmed-meshheading:3137465-Cricetinae, pubmed-meshheading:3137465-DNA, pubmed-meshheading:3137465-DNA Repair, pubmed-meshheading:3137465-Dimethyl Sulfoxide, pubmed-meshheading:3137465-Female, pubmed-meshheading:3137465-Haplorhini, pubmed-meshheading:3137465-Humans, pubmed-meshheading:3137465-Liver, pubmed-meshheading:3137465-Male, pubmed-meshheading:3137465-Mice, pubmed-meshheading:3137465-Rats, pubmed-meshheading:3137465-Species Specificity
pubmed:year
1988
pubmed:articleTitle
Induction of unscheduled DNA synthesis in primary cultures of rat, mouse, hamster, monkey, and human hepatocytes.
pubmed:affiliation
Department of Cellular and Genetic Toxicology, SRI International, Menlo Park, CA 94025.
pubmed:publicationType
Journal Article, Comparative Study