Structure activity studies on the induction of peroxisomal enzyme activities by a series of phthalate monoesters in primary rat hepatocyte cultures.
A series of 9 phthalate monoesters were cultured with primary rat hepatocytes for 70 h and their effect on peroxisomal fatty acid beta-oxidation (palmitoyl-CoA oxidation) determined. Marked quantitative differences in the induction of enzyme activity were observed with both alkyl chain length and position of side chain substitution affecting compound potency. With all 9 compounds a good correlation was observed between electronic structural parameters obtained by molecular orbital calculations and biological activity in the cell culture system. These results demonstrate a relationship between chemical structure and biological activity for a series of phthalate monoesters and indicate the potential usefulness of primary hepatocyte cultures to screen compounds for peroxisome proliferation.
Lake
B G
BG
Lewis
D F
DF
Gray
T J
TJ
Beamand
J A
JA
Hodder
K D
KD
Purchase
R
R
Gangolli
S D
SD
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008830:Microbodies / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000378:metabolism*; D010795:Phthalic Acids / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship
D000214:Acyl Coenzyme A; D010795:Phthalic Acids; D010171:Palmitoyl Coenzyme A