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Ultrastructural Changes in the Mitochondria of Intestinal Epithelium of Rodents Treated with Methylglyoxal-bis(guanylhydrazone)¹

Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14263 [T. C. M., C. W. P.], and Department of Natural Sciences, Daemen College, Amherst, New York 14226 [A. P.]

² To whom requests for reprints should be addressed.

Ultrastructural studies of rats or mice treated for 24 hr with a toxic dose (100 mg/kg) of methylglyoxal-bis(guanylhydrazone) revealed the presence of damaged mitochondria in the crypt cells of the intestinal epithelium. Mitochondria were severely swollen and electron lucent, and appeared to be similar to those observed previously in a variety of cell types treated in vitro and in vivo with methylglyoxal-bis(guanylhydrazone). Since thymidine incorporation into the intestine was not found to be decreased until after 24 hr, it is concluded that the mitochondrial damage of methylglyoxal-bis(guanylhydrazone) could be responsible for the antiproliferative toxicities of the drug.

¹ This investigation was supported by Research Grant CA 22153 and Core Grant CA 24538 from the National Cancer Institute, Department of Health, Education and Welfare.

Received 2/18/82. Accepted 10/21/82.

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