Natural killer sensitivity of tumor cells isolated from primary and metastatic lesions of four Bomirski melanoma variants.

Natural killer (NK) sensitivity of melanoma cells isolated from primary and metastatic lesions of four Bomirski melanoma variants was compared. The hamster melanomas differed in their growth rate and metastatic pattern. We found that during tumor growth of all the variants tested, NK sensitivity of melanoma cells at the metastasis formation stage was significantly lower in both primary and metastatic tumors than in cells isolated from primary tumors at transplantation.

Hypothesis: possible role for the melatonin receptor in vitiligo: discussion paper.

A new unifying hypothesis for the aetiology of vitiligo is proposed, in which we postulate that the final destruction of melanocytes in vitiligo results from a cascade of reactions initiated by a disregulation of melanogenesis, caused by activation of the melatonin receptor. These events result in the high and uncontrolled production of free radicals and toxic products of melanogenesis which sequentially damage or destroy melanocytes and keratinocytes, provoke an autoimmune response against exposed intracellular or altered cell surface antigens, and increase the propensity of melanocytes to undergo malignant transformation.

Natural killer sensitivity of four Bomirski melanoma variants.

The sensitivity of four hamster melanoma variant cells to natural killer (NK) cell lysis mediated by hamster blood and spleen mononuclear cells is examined. The melanoma variants differed in their differentiation level, growth rate, and frequency and localization of metastases. The cells of the melanoma variants were found to differ in their sensitivity to NK cell mediated lysis.

The natural history of a family of transplantable melanomas in hamsters.

We have characterized a family of transplantable melanomas in Syrian (golden) hamsters, which originated in 1959 as a spontaneous melanoma of hamster skin, and which has been maintained since then by serial passage. Emphasis has been placed on using the same method of transplantation, keeping strict records on all passages, and applying the same investigative techniques, in order to trace tumor behavior over long periods of time. This tumor family consists of five variants linked by common origin, but which differ with respect to differentiation level, malignancy, intermediary metabolism, chromosome number, and cell surface properties.

Positive regulation of melanin pigmentation by two key substrates of the melanogenic pathway, L-tyrosine and L-dopa.

We describe results demonstrating the positive regulation of melanogenesis by two substrates of the melanogenic pathway. We have found that L-tyrosine and L-dihydroxyphenylalanine (L-dopa), whose metabolic fates are affected by the activity of that pathway, can also act as its regulators. In living pigment cells, tyrosinase (EC 1.

Chromosome changes associated with spontaneous phenotypic variation of transplantable melanoma.

The chromosome constitutions of black-melanotic (Ma), brown-melanotic (MI), and amelanotic (Ab) melanomas of the Syrian hamster were compared. The MI and Ab melanomas arose through a spontaneous phenotypic alteration of the Ma tumor. All three variants differ in their growth rates, with MI showing the slowest, Ab the fastest, and Ma intermediate growth rate.

Ultrastructural aspects of melanization of hamster Ab amelanotic melanoma in primary cell culture.

When the hamster Ab amelanotic melanoma has been grown as subcutaneous transplants in hamsters, melanin and identifiable melanosomes have never been observed by electron microscopy. When the cells were placed in primary cell culture, melanosomes of a granular type which contained small amounts of melanin appeared during the first 24 hours of cell culture. As the cultures grew older, the number and degree of melanization of the melanosomes increased, and eventually after 3-5 days they were found in all melanoma cells.

Phenotypic changes of Ab hamster melanoma during long-term culture.

Cells of the Ab hamster amelanotic melanoma in primary cell culture have previously been shown to melanize rapidly, detach from the glass substratum and lose the ability to proliferate in vitro. Recent work demonstrates that when the Ab cells are subcultured prior to a complete loss of proliferative ability, the above processes occur in the 1-3 passages. In about half of our attempts, long-term cultures of Ab cells could be established from the few cells which remained attached to the glass during one of these first passages and resumed proliferation after a several-week period.

Metabolic characterization of three hamster melanoma variants.

Some enzyme activities and metabolic features of the black Ma melanotic, brown MI melanotic and Ab amelanotic melanomas of hamster were investigated. The activities of hexokinase and phosphofructokinase were similar in all three melanomas, the activity of NAD-dependent glycerol-3-phosphate dehydrogenase was higher in the amelanotic melanoma and that of pyruvate kinase and lactate dehydrogenase were slightly lower in MI than in the other tumors. The activities of citrate synthase, succinate dehydrogenase and malate dehydrogenase were higher in the Ma and MI melanotic melanomas than in the Ab amelanotic melanoma.

Effects of actinomycin D and cycloheximide on the increase in tyrosinase activity of hamster amelanotic melanoma cells in vitro.

Tyrosinase activity in the Ab hamster amelanotic melanoma cells cultured in serum-free Eagle's MEM increased 3 times after 6 h of primary cell culture. This increase was inhibited completely by cycloheximide, while actinomycin D had no effect on this process. After 24 h of culture in MEM with calf serum, further increase of the tyrosinase activity was inhibited by both cycloheximide and actinomycin D.

Biochemical characterization of three hamster melanoma variants--II. Glycolysis and oxygen consumption.

Lactate production and oxygen consumption were studied in single cell suspension prepared from solid tumours of the black-melanotic (Ma), brown-melanotic (MI) and amelanotic (Ab) melanomas of hamster. Aerobic lactase production was about 5 times higher in the fast growing Ab melanoma than in the slow growing Ma and MI melanomas. Aerobic lactate production in both melanotic hamster melanomas was stimulated by 3-(3,4-dihydroxyphenyl)-L-alanine.

Effect of tissue selection on melanization of MI hamster melanoma.

Selection of the most melanized tissue of the slightly melanotic MI melanoma in hamster resulted in an origin of a new highly melanotic tumor line. It differed from the parental MI melanoma in the 5-fold higher melanin content, but its tyrosinase activity, growth rate and histological structure remained unchanged. Selection of the least melanotic tissue of the MI melanoma did not give positive results.

Biochemical characterization of three hamster melanoma variants--I. Tyrosinase activity and melanin content.

Tyrosinase activity in the soluble fraction of the cells and melanin content in the whole cells of the black-melanotic (Ma), brown-melanotic (MI) and amelanotic (Ab) hamster melanomas were studied. The activity of the soluble tyrosinase was highest in MI lower in Ma, and very low in Ab melanoma. Melanin content was greatest in the Ma, lower in MI, and none in Ab melanoma.

Tyrosinase activity in primary cell culture of amelanotic melanoma cells.

After transfer of the Ab amelanotic melanoma cells from in vivo to in vitro growth conditions tyrosinase activity in their soluble fraction rapidly increased. This increase lasted to the middle of the logarithmic phase of growth and was followed by a decrease of tyrosinase activity, which was accompanied by accumulation of melanin in the cells. Calf serum stimulated simultaneously tyrosinase activity, melanin synthesis, and proliferation of the melanoma cells.

Concanavalin A induced agglutinability of the isolated cells of hamster melanotic and amelanotic melanomas.

The agglutination of cells isolated from solid melanotic and amelanotic malanomas in hamsters by Concanavalin A was studied. It has been found that the agglutination intensity of the two kinds of melanoma cells was different and depended on the concentration of the lectin. It has been suggested that the different susceptibility of the cells to Concanavalin A is related to changes of surface glycoproteins, resulting from a spontaneous alteration of the melanotic melanoma into amelanotic one.

Surface glycoprotein components in isolated melanotic melanoma cells in the golden hamster.

A study of glycoprotein components in trypsin-digested material from the surface of isolated melanotic melanoma cells showed presence of amino sugars, protein-bound hexoses, fucose and sialic acids. The high content of fucose and low content of sialic acids in the surface material from the cells were striking.

Comparison of the surface glycoprotein components in the isolated cells of hamster melanotic and amelanotic melanomas.

A suspension of melanoma cells isolated non-enzymatically from tumors (melanotic and amelanotic) of transplantable melanoma in Syrian hamster was treated with trypsin to obtain surface material. In the material released from the cell surface contents of protein, aminosugars, fucose, sialic acids and hexoses were determined. Differences in the composition of the surface material derived from two kinds of melanoma were observed.