Mutagenic Effects Of

In the past, the classic experimental animal for the study of genetic mutations has been the banana fly, Drosophila melanogaster. Several studies exist in which the effect of LSD on genetic mutation has been observed in this fly. Grace, Carlson and Goodman (44) studied the mutagenic effects of intra-abdominal injections of LSD in concentrations ranging from 1 to 500 micrograms per cc. They have not found an increase in induced mutations in the LSD-treated group. On the basis of these negative findings, the authors consider it improbable that LSD induces mutation in humans. Markowitz, Brosseau and Markowitz (74) fed LSD to male flies in concentrations of 100, 5,000 and 10,000 micrograms per cc. In this experiment, LSD produced a significant increase in the frequency of sex-linked recessive lethal mutations. The authors concluded that LSD at high concentrations is a weak mutagen in Drosophila.

In several studies performed in Drosophila flies, lower concentrations of LSD had no mutagenic effects, but an increased frequency of induced mutations was observed after excessive dosages. Vann (111) reported that dosages of 24,000 micrograms per kg produced no significant increase in the frequency of recessive lethals, whereas a dosage of 470,000 micrograms per kg did. Browning (15) administered intraperitoneal injections of 0.3 microliters of a solution containing 10,000 micrograms per cc of LSD; this dosage corresponds to about 4,000,000 micrograms per kg of body weight. Out of seventy-five flies, only fifteen survived this procedure, and ten were fertile. Under these circumstances, a significant increase in recessive lethal mutations in the X-chromosome of male flies was observed by the author. A 1:1 dilution of the original solution, when injected into one hundred males, resulted in thirty-five survivors of which thirty were fertile; the frequency of mutations markedly dropped. Srdtn (101) concluded on the basis of his experiments with LSD in the Drosophila fly that LSD is a weak mutagen producing gene and chromosome mutations only when used in very high concentrations; this finding is in basic agreement with the existing literature on the mutagenic effects of LSD.

The effects of LSD were also tested on another standard genetic system, namely the fungus Ophistoma multiannulatum. Zetterberg (118) exposed the cells of this fungus to 20-50 micrograms per cc of LSD; he did not find any difference between treated and control cells. The data on Drosophila flies and fungi suggest that LSD is a weak mutagenic agent that is effective only in doses far exceeding those commonly used by human subjects.

There are several interesting studies focusing on the interaction of LSD with deoxyribonucleic acid (DNA) and ribonucleic acid (RNA); these studies could contribute to our understanding of the mechanism of interaction between LSD and the chromosomes or genes. Yielding and Sierglanz (115), using spectrophotometric methods, were able to demonstrate binding of LSD, its inactive optical isomer, and its inactive brominated analogue by helical DNA of the calf thymus. Binding did not take place with yeast RNA or nonhelical DNA, suggesting that this binding is specific for helical DNA.

Wagner (112) concluded on the basis of his experiments that LSD interacts directly with purified calf thymus DNA, probably by intercalation, causing conformational changes in the DNA. According to him, it is unlikely that this could influence the internal stability of the DNA helix enough to cause chromosomal breakage. However, it may lead to the dissociation of histones, which could render DNA susceptible to enzymatic attack. Smythies and Antun (98) performed similar experiments and arrived at the conclusion that LSD binds to nucleic acids by intercalation. According to Dkhotsky et al., (28) this evidence of LSD intercalation into the DNA helix provides a clue to the physical mechanism involved in the mutagenic effects of high doses of LSD in Drosophila and the fungus, as reviewed above.

Nosal (83) investigated the effects of LSD on the Purkinje cells of the cerebellum of growing rats. These studies were specifically focused on the action of the ribonucleoproteins (RNP) of the differentiating nucleus-ribosoine system. Only large doses of LSD (100-500 micrograms per kg) seemed to induce changes in the structure and staining properties of this cellular system.

Obviously, much inore research is needed for the final clarification of the interesting interaction between LSD and various chemical substances involved in the genetic mechanisms.

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