Cytotoxicity and metabolism of alkyl phospholipid analogues in neoplastic cells.

摘要: The cytotoxic response of several types neoplastic cells to analogues unnatural alkyl phospholipids (e.g., rac-1-hexadecyl-2-methoxy-glycero-3-phosphocholine) has been partially attributed their accumulation as a result the low activity cleavage enzyme (a tetrahydropteridine-dependent monooxygenase) in tumor cells. We tested this possibility by comparing that exhibit differences sensitivity toward effects rac-1-hexadecyl-2-methoxy-glycero-3-phosphocholine. Human promyelocytic leukemia (HL-60), cell line highly sensitive phospholipid analogue, possessed an (0.25 pmol/min/microgram protein) similar found three known be relatively resistant analogue: immature human promyeloblastic (K562) (0.22 protein), polymorphonuclear neutrophils (0.34 and Madin-Darby canine kidney (0.37 protein). Moreover, our results indicate rac-1-octadecyl-2-methoxy-glycero-3-phosphocholine analogue is not substrate for with active microsomal preparation from rat liver; was 200-fold less than rate obtained 1-octadecylglycerol substrate. In cultures either or type cells, approximately 90% added rac-1-[9',10'-3H]octadecyl-2-methoxy-glycero-3-phosphocholine metabolized during 24-h incubation. amount radiolabel fatty acids, major product activity, small, essentially identical amounts were produced all four [3.1 +/- 0.2% (SD)]. These data cellular activities are responsible differential responses between normal specific rac-1-octadecyl-2-methoxy-glycero-3-phosphocholine. On other hand, uptake could factor explaining certain since more radiolabeled 1-octadecyl-2-methoxy-glycero-3-phosphocholine associated susceptible HL-60 types. Autoradiography revealed 2-methoxy accumulates at periphery whereas label uniformly distributed K562 cells.(ABSTRACT TRUNCATED AT 400 WORDS)