Activity of a new nitrosourea (TCNU) in human lung cancer xenografts.
The activity of a new nitrosourea (TCNU) based on the endogenous amino acid taurine was assessed in three human lung cancer xenografts growing in immunodeficient mice. Moderate activity (specific growth delays of 0.63 and 1.13 compared with controls) was seen in two non-small cell tumours after a single oral administration of 20 mg-1kg. This dose was curative in a small cell xenograft. By using high performance liquid chromatography it was possible to detect parent drug in the tumours as well as the plasma and tissues after oral administration of TCNU. Drug sensitivity was correlated inversely with the amount of the DNA repair enzyme 0(6)-methylguanine-DNA methyltransferase assayed from extracts of the tumour cells but not with the levels of parent drug within the tumour. This compound appears to have unique pharmacokinetic properties compared with other chloroethylnitrosoureas.
Fergusson
R J
RJ
University Department of Clinical Oncology, Western General Hospital, Edinburgh, UK.
Anderson
L E
LE
Macpherson
J S
JS
Robins
P
P
Smyth
J F
JF
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001984:Bronchial Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011088:DNA Ligases / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D009607:Nitrosourea Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013654:Taurine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea; D011088:DNA Ligases