Alkyl phosphocholines: toxicity and anticancer properties.
The study reports on the investigation of acute and subacute toxicity and on antineoplastic activity of hexadecylphosphocholine (HPC), the first compound of a new class of antineoplastic chemotherapeutics. In rats, the LD50 of HPC was 606 mumol/kg; the maximum tolerable dose over four weeks was 39 mumol/kg. Symptoms of toxicity were enteritis, spider cell activation in the liver, hemosiderosis in the spleen and reversible transaminase increase. The best therapeutic effect was observed on methylnitrosourea (MNU)-induced mammary carcinoma in the rat. Two transplantable mammary carcinomas in the rat and autochthonous benzo(a)pyrene-induced sarcomas exhibited low-grade sensitivity to HPC. The MXT mammary carcinoma of the mouse, the Walker 256 carcinosarcoma of the rat, and autochthonous acetoxymethylmethylnitrosamine-induced colonic tumors of the rat were not chemosensitive to HPC.
Muschiol
C
C
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Berger
M R
MR
Schuler
B
B
Scherf
H R
HR
Garzon
F T
FT
Zeller
W J
WJ
Unger
C
C
Eibl
H J
HJ
Schmähl
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D002277:Carcinoma / Q000188:drug therapy; D002794:Choline / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D010742:Phospholipid Ethers / Q000627:therapeutic use* / Q000633:toxicity; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C039128:miltefosine; D002794:Choline