Enhancement of L-dopa incorporation into melanoma by dopa decarboxylase inhibition.
Melanoma cells possess a special biochemical pathway for the conversion of L-dopa to melanin. Selective incorparation of exogenous L-dopa into melanoma cells in vivo has been limited by extensive decarboxylation to dopamine. Pretreatment of animals bearing the S-91 Cloudman or ACI melanomas with Ro4-4602, a potent dopa decarboxylase inhibitor limited incorporation of label into adrenal tissue and enhanced entry of label into tumor. Six hours following pretreatment, the ratio of tumor to adrenal specific activities was altered from 0.25 to 1.5 for the S-91 melanoma and 0.68 to 1.99 for the ACI melanoma indicating diversion of metabolism away from catecholamine formation. The possibility of a selective diagnostic and/or therapeutic approach is proposed.
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology; D002395:Catecholamines / Q000096:biosynthesis; D007980:Levodopa / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000378:metabolism; D051381:Rats
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002395:Catecholamines; D008543:Melanins; D007980:Levodopa; D001545:Benserazide