Comparative study on the influence of two 2-chloroethylnitrosoureas with different carbamoylating potential towards glutathione and glutathione-related enzymes in different organs of the rat.
The influence of two CNUs with similar alkylating but strongly different carbamoylating activity towards the glutathione system was investigated in different organs. Both CNUs influence the glutathione system of the bone marrow in a similar manner, irrespective of their carbamoylating potential. In contrast, glutathione reductase activity in the other organs was strongly decreased by the potent carbamoylator BCNU, whereas no or only minor effects were produced by its weakly carbamoylating counterpart HECNU. The results confirm that bone marrow toxicity of CNUs primarily results from alkylation and not from carbamoylation. Other organ-related toxic effects, however, are probably a result of carbamoylating reactions exerted by BCNU. This applies especially to lung toxicity that has been observed frequently as a major side effect in clinical trials with BCNU.
Stahl
W
W
Department of Food Chemistry and Environmental Toxicology, University of Kaiserslautern.
Eisenbrand
G
G
D000478:Alkylation; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002330:Carmustine / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009607:Nitrosourea Compounds / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D009607:Nitrosourea Compounds; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; C013876:elmustine; D002330:Carmustine