Abstract
We described elsewhere that the synergistic antitumor activity of endotoxic extracts from Re mutants of gram-negative bacteria and trehalose mycolate against guinea pig syngeneic line 10 tumor was abrogated after peptidic substances accompanying these extracts had been removed. This activity could be restored by combining peptide-free endotoxin either with cell wall skeleton from Bacillus Calmette-Guérin, a polymeric mycolic acid-arabinogalactan-mucopeptide complex, or with a combination of two separate components, trehalose dimycolate and N-acetylmuramyl-l-alanyl-(l-seryl)-d-isoglutamine (MDP). We report here that when a combination of endotoxin (150 µg) and a mixture of MDP (150 µg) and trehalose dimycolate (150 µg) was inoculated into established dermal tumors, a significant number of the animals died, presumably of endotoxic shock. All surviving animals suffered severe but temporary lethargy. When administered alone intradermally in the dose levels tested, none of the components caused severe lethargy or lethality. The lethal effects of 150 µg of MDP also occurred in combination with relatively weak endotoxic products, such as Pseudomonas vaccine (Pseudogen), and these effects did not depend upon the presence of malignant tissue. Guinea pigs inoculated i.v. were even more susceptible inasmuch as the addition of as little as 6 µg of MDP to 150 µg of Pseudogen, itself not lethal, caused the death of 80% of the animals.
Footnotes
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↵1 To whom requests for reprints should be addressed.
- Received June 4, 1979.
- Accepted September 4, 1979.
- ©1979 American Association for Cancer Research.
Volume 39, Issue 11
