Mechanisms of ascorbic acid-induced inhibition of chemical transformation in C3H/10T1/2 cells.
Ascorbate irreversibly inhibited morphological transformation induced by methylcholanthrene in C3H/10T1/2 cells. To determine the mechanisms of this inhibition, we studied ascorbate uptake, redox potential, matrix proteins, and lipid composition of 10T1/2 cells. Ascorbate (16.8 nmol/dish) saturated cells and reduced the NADH-to-NAD+ ratio. Daily treatments with ascorbate, 28 nmol/dish, maintained intracellular ascorbate and reduced NADH by half. Matrix collagen and glycoproteins were stimulated by ascorbate, Iso-ascorbate, and dehydroascorbate in a dose-dependent manner. Both ascorbate and dehydroascorbate reduced total lipids with time; neutral lipids increased but were released into the media, phospholipids were modified, cholesterol-phospholipid ratios declined, and an inverse relationship between unsaturation index and cholesterol-phospholipids was apparent. Lipophilic bodies gradually accumulated. Our data suggest that inhibition of transformation by ascorbate, Iso-ascorbate, or dehydroascorbate may be associated with regulation of the redox potential, glycoproteins, and lipids in 10T1/2 cells.
Ibric
L L
LL
Children's Hospital of Los Angeles, CA.
Peterson
A R
AR
Sevanian
A
A
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D008748:Methylcholanthrene / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
D009243:NAD; C005056:isoascorbic acid; D008748:Methylcholanthrene; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid