Melanoma Induction Research Articles

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: VII genic mechanisms

The expression of embryonic phenotypic entities induced by a variety of carcinogenic agents can be unified by proposing a process of deheterochromatization. This central process can occur from purely genetic recombinations through the phenomenon of “position effect” of certain new gene proximities near facultative heterochromatin. The same effect may occur through genetic recombinations of Mendelian traits exemplified by the induction of melanomas in platy-swordtail hybrids or by specific chromosomal alterations through mechanisms of translocations, etc. as seen in human leukemias. It is further proposed that some of these chromosomal alterations involve the “turning on” of sarc-like genes i.e. protein phosphokinases which in turn cause alterations in the chromatin construct of further heterochromatic areas thus leading to a cascade phenomenon as discussed previously. (1). Viral processes also would be categorized in this latter mode since they would introduce aberrant protein phosphokinase genes into the cell. An entirely different origin of dehetero-chromatization would be achieved by such agents as ethionine. Ethionine is known to react with adenosine triphosphate to produce S-adenosyl-ethionine. This compound interferes with normal methylation reactions and produces hypomethylated transfer ribonucleic acid and deoxyribonucleic acid. Hypomethylated deoxyribonucleic acid has been correlated with the activation of globin genes. The mechanism may include the same deheterochromatization process although the choice between hypomethylated proteins which may also exist in these states or hypomethylated deoxyribonucleic acid as being basic to this mechanism, cannot be made. This hypothesis will explain how heredity can be a factor similar to other carcinogenic events. Furthermore it may explain processes such as the synergism between viruses and carcinogens. This unified theory would predict that the position effect may cause carcinogenic events only if the protein phosphokinase gene is involved. It would also require that protein phosphokinase genes are redundant and occur near or at the specific chromosomal anomalies described thus far. Minor isologous transfer ribonucleic acids are probably the result of modifications of minor nucleotides and, at least for the methylated subset of these, amy involve embryonic genes (2). This process appears to present transcriptional control mechanisms with an anomaly such that the overall phenotype of the embryo becomes expressed which includes further (embryonic) features of control. Other chemicals may modify heterochromatin by intercalation causing a “pseudo-position effect” or chemicals such as the drug phenobarbital, a tumor promotor, may induce certain enzymic changes, such as protein methylation or hydroxylations that result in the same chromatin alterations alluded to previously. Still other chemicals, the mutagenic and alkylating agents, could cause alterations similar to those induced by anomalous enzymic bioalkylations. Steroids as carcinogens have already been described in terms of “groove distorters” (3). Such a process fits well with a process of deheterochromatization. Deoxyribonucleic acid alterations such as those that would occur during groove distortion should result in hierarchical structural chromatin changes. However, the theory does not predict several features of carcinogenesis such as latency and certain requirements of chronic administration of carcinogenic agents.

Speculations on the role of ultraviolet radiation in the development of malignant melanoma.

Interest in the etiology of human malignant melanoma has increased considerably in recent years. The basis for this heightened concern can be attributed to two seemingly unrelated issues. The first is that the incidence of malignant melanoma is increasing at an alarming rate. At the present time, both the incidence of melanoma and the mortality rate are doubling every 10 to 17 years. Thus identification of causal factors in the development of melanoma is an urgent necessity if this upward trend is to be curbed. The second issue that has directed attention to the identification of etiologic factors in malignant melanoma is ozone depletion. The layer of ozone surrounding the earth shields it from solar uv radiation. Anticipated decreases in stratospheric ozone, resulting from high-altitude aircraft, nuclear explosions, and the release into the atmosphere of chlorofluoromethanes from refrigerants and aerosol sprays, raised concerns about the effects of an increased exposure of all life forms to uv light. One anticipated effect of increased exposure of humans to uv light is a corresponding increase in some types of skin cancer in humans. If malignant melanoma is included among the types of skin cancer at risk of increasing, then the impact of ozonemore » depletion on humans is serious indeed. In the prognosis for melanoma is less favorable, particularly in cases in which the tumor is already invasive at the time of diagnosis. Thus the threat of an increased level of exposure to light has stimulated a careful reevaluation of the role of radiation in the induction of melanoma.« less

Levodopa Therapy and Malignant Melanoma

Concern has been voiced over a role for levodopa in the induction or stimulation of growth of cutaneous malignant melanoma. Prospective query of 1,099 patients of the Melanoma Clinical Cooperative Group at the time of presentation of their primary melanoma showed only one patient who had been taking levodopa. It was concluded that levodopa, if a factor in the induction of melanoma, must be playing an inconsequential role in the rapid rise in incidence observed for this tumor over the past decade.

Amino acid pattern and malignant growth

In a study on the genetic induction of melanoma in hybrids of poeciliidae the pattern of free amino acids was found richer and more acidic in tumour-disposed fish than in others. Changes in the amino acid level are accompanied by changes in the growth of the melanoma, independent of whether the amino acid change is determined by genetic constitution or by environmental conditions. All hybrids which produce melanomas have the high concentration of free amino acids before tumour formation; later it decreases, acidic amino acids dominating throughout (25–65% taurine). In a second free amino acid study on plants containing cancerostatic protein fractions an almost complementary pattern was found, the dominating compound being arginine (35%). The cancerostatic protein fraction is also basic. It is active only in the native state; inhibition may be compensated by DNA. In both studies an influence (one acting in the opposite direction to the other) on the attachment of histone to the nucleic acids is suggested.