Fine Structural Alterations in Cell Particles During Chemical Carcinogenesis : II. Further Evidence for Their Involvement in the Mechanism of Carcinogenesis. The Swelling of Rat Liver Mitochondria During Feeding of Amino Azo Dyes

Swelling under carefully controlled conditions has been used to study alterations in the structure of rat liver mitochondria as a result of feeding azo dyes. The changes of the swelling properties of the mitochondria during feeding of the hepatocarcinogenic 3'-methyl-4-dimethylaminoazobenzene are essentially comparable to those observed previously with the microsomes, under the same dietary conditions. These alterations in mitochondrial swelling are not related to changes in the amount of these cell particulates per unit weight of tissue, during feeding of this azo dye. As with the microsomes, feeding of the isomeric but relatively noncarcinogenic 2-methyl-4-dimethylaminoazobenzene does not affect swelling. The structural differences between liver and hepatoma mitochondria show up not only in the rate and extent of swelling but also in the form of the curves of pH dependence. The influence of ketones and sulfhydryl compounds on the swelling of normal liver mitochondria were studied, with particular emphasis to the role of sulfhydryl groups in membrane permeability. The sudden steep rise in the tumor incidence in groups of rats fed 3'-methyl-4-dimethylaminoazobenzene for increasing intervals of time occurs at about 4 weeks. This time correlates with the point of the minimum swelling of microsomes and mitochondria isolated from the livers of rats fed this same dye. Thus, a correlation is established between the alterations of the swelling properties of these particulates and the carcinogenic process.     

CLINICAL OBSERVATIONS ON IPRONIAZID IN IDIOTS WITH EPILEPSY

In contradistinction to the observation made before that iproniazid has a potentiating effect on certain amines in guinea pigs, human studies have shown that this effect has very little clinical importance, when both the amines and the amine oxidase inhibitor are given in the usual therapeutic doses. However, neither in man nor in the guinea pig pretreatment with iproniazid showed a potentiating effect on amines which are not substrates of monoamine oxidase (ephedrine and amphetamine). Patients with epilepsy and allergic disease may receive iproniazid.     

Pigment,abnormal mitochondria and laminar bodies in human sympathetic neurons

Summary A study was made of the fine structure of neurons in lumbar sympathetic ganglia which were surgically removed from a 52 year old male patient. Some samples were fixed by direct immersion into osmium tetroxide, others were first prefixed with an aldehyde solution. Large vesiculated pigment granules were described, compared with similar particles, previously seen in human and animal autonomic neurons, and their glycogen and lipid-soluble components were tentatively identified. These granules increase numerically during aging, are probably derivatives of lysosomes, and may incorporate both lipofuscin and melanin in the same particle. Mitochondrial changes (enlargement, disappearance of cristae and deposit of opaque central material) in sympathetic perikarya occurred under all conditions of preservation, and were interpreted as hypoxia-induced structures which developed during life. Abnormal aggregates of mitochondria were seen in nerve processes. Laminar bodies, chiefly associated with mitochondria were present, especially, in aldehyde prefixed material. It remained undecided whether these structures occurred during life or were artifacts. Compared with direct osmium tetroxide fixation, prefixation with aldehyde, followed by osmium tetroxide proved to be a superior, but not entirely adequate method of preserving deep layers of neuronal tissue. This investigation was supported (in whole) by United States Public Health Service Grant NB 1879-09, Institute for Nervous Diseases and Blindness.The author is greatly indebted to Dr. Jere W. Lord, Jr., Department of Surgery, New York University Medical Center, for the surgically removed tissues used in this study; he is grateful to Dr. Sanford L. Palay, Department of Anatomy, Harvard Medical School, for suggesting the use of the then unpublished method of prefixation with the aldehyde solution. It is a pleasure to acknowledge the expert skill with which Miss Carmen DeLemos and Mr. Arnlod Cianella assisted in completing this work.