Toxic oil stimulates collagen synthesis acting at a pretranslational level in cultured fat-storing cells.
OBJECTIVE
The toxic oil syndrome appeared in Spain in 1981 as a result of ingestion of rapeseed oil denatured with aniline. Some patients developed scleroderma-like skin lesions and liver cirrhosis. Mechanisms of these fibrotic lesions are not known. The present study was designed to investigate the effect of toxic oils on collagen metabolism.


METHODS
We measured the relative rate of collagen production, absolute rate of collagen synthesis, production, secretion, and degradation, proline transport, steady-state levels of procollagen alpha 1(l)-messenger RNA (mRNA) in cultured fat-storing cells, and chloramphenicol acetyltransferase activity in transfected cells.


RESULTS
Toxic oils increased collagen synthesis, procollagen alpha 1(l)-mRNA levels, and chloramphenicol acetyltransferase activity in cultured fat-storing cells. Effect on collagen production correlated with lipid peroxide content in oils. Cycloheximide, alpha-tocopherol, and methylene blue prevented the increase in procollagen alpha 1(l)-mRNA. Oleylanilide and linoleylanilide, markers for toxic oils, reproduced the stimulatory effects of toxic oils on collagen production and procollagen alpha 1(l)-mRNA.


CONCLUSIONS
Toxic oils increased collagen synthesis by acting on the promoter of procollagen alpha 1(l) gene, probably through lipid peroxides derived from acylanilides. We suggest that toxic oil may have stimulated procollagen gene expression through the formation of adducts of aldehydes with some transcription factor.
Hernández-Muñoz
I
I
Centro de Investigación, Hospital Universitaro Doce de Octubre, Universidad Complutense, Madrid, Spain.
de la Torre
M P
MP
Pedraza
M A
MA
Sánchez-Alcázar
J A
JA
Muñoz-Yagüe
M T
MT
Solis-Herruzo
J A
JA
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001937:Brassica; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005229:Fatty Acids, Monounsaturated; D006706:Homeostasis; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009821:Oils / Q000633:toxicity*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010938:Plant Oils / Q000506:poisoning*; D011347:Procollagen / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D000074262:Rapeseed Oil; D051381:Rats
D000813:Anilides; D005229:Fatty Acids, Monounsaturated; D008041:Linoleic Acids; D009821:Oils; D009829:Oleic Acids; D010938:Plant Oils; D011347:Procollagen; D012333:RNA, Messenger; D000074262:Rapeseed Oil; D019301:Oleic Acid; D003094:Collagen; D019787:Linoleic Acid