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A variety of cell lines have been prepared by fusion of the murine WEH1 3B cell line with peripheral blood leukocytes from a patient with chronic granulocytic leukemia. Fusion products were selected for their ability to produce a leukemia-associated antigen (CAMAL) previously described. One such line which originally produced CAMAL subsequently lost this ability and was used as a negative control. A number of antibodies were conjugated to hematoporphyrin (HP) and tested for their ability to bind to cell lines as detected by either fluorescence or by their ability to kill cells after light activation. The antibodies used were: rabbit anti-Hu (a conventional rabbit antiserum raised to membrane preparations from normal human peripheral blood leukocytes which served as a positive control); CAMAL-1 (a monoclonal gamma 1 antibody with specificity for the CAMAL antigen); and L1210 (an irrelevant monoclonal gamma 1 antibody). HP was conjugated to the antibodies by a carbodiimide procedure. When labeled cells were examined by fluorescence microscopy, it was apparent that both the rabbit antibody and CAMAL-1:HP showed positive labeling. The ability of the antibody:HP conjugates to kill labeled cells following light activation was tested. It was shown that rabbit anti-Hu:HP and CAMAL-1:HP conjugates were capable of killing significant numbers of cells when HP concentrations were as low as 1.2 ng/10(6) cells, whereas similarly treated cells exposed to either L1210:HP or HP alone did not exhibit significant killing until concentrations reached 240 and 120 ng/10(6) cells, respectively. Further experiments in which other cell lines were tested, all at HP concentrations of 12 ng/10(6) cells, demonstrated that those lines producing CAMAL were killed, whereas negative lines were not.

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The term "photoimmunotherapy" describes an anti-cancer treatment that combines the phototoxic effects of chemical such as hematoporphyrin and the target-seeking ability of antibodies. Hematoporphyrin was chemically coupled to monoclonal antibodies directed to the DBA/2J myosarcoma M-1. Administration of anti-M-1-hematoporphyrin conjugates i.v. to M-1 tumor-bearing animals followed by exposure to incandescent light resulted in suppression of M-1 growth. The time interval between injection and light exposure was an important parameter in terms of tumor suppression. Tumor-bearing animals maintained in the dark for 96 to 196 hr after hematoporphyrin-antibody injection followed by 4-hr light exposure demonstrated significantly lower tumor incidence and longer latency periods, in comparison to conjugate-treated animals instantly exposed to light. The growth inhibiting properties of the conjugate appeared to be M-1-specific; it had no effect on the growth of a C57BL/6J lymphoma EL4. In addition, conjugates made with a nonspecific monoclonal antibody did not have any specific anti-tumor effect on M-1 growth. Treatment with equivalent doses of hematoporphyrin or antibody had no significant inhibiting effect on tumor growth. Clearly, the homing ability of the specific monoclonal antibody-hematoporphyrin conjugate was essential for effective drug delivery and inhibition of tumor growth.

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Dehydroevodiamine isolated from Evodiae Fructus lowered blood pressure with bradycardia in anesthetised rats. At a cumulative dose of 22.5mg/kg/30min, there was a very significant decrease in blood pressure and heart rate. There was a more important decrease in diastolic pressure than systolic pressure, implying a vasodilatory effect. The hypotensive effect of dehydroevodiamine can be abolished partly by indomethacin and more completely, polyphoretin phosphate. It is suggested that the hypotensive effect of dehydroevodiamine may be mediated through prostaglandin synthesis. A similar action mechanism in dehydroevodiamine-stimulated rat uterus contraction is also discussed.

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Ethanolic extracts of forty-four commercial herbal drugs and two fresh plants used in folk medicine, all species of the Asteraceae, were examined for their phototoxic and antibiotic activities against Escherichia coli, Saccharomyces cerevisiae and Candida albicans. Twenty samples were found to be active as either phototoxic and/or antibiotic agents and their phototoxic effects correlate with the presence of polyacetylenes and thiophenes.

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alpha-Terthienyl and 5 polyacetylenes were examined for chromosome damaging activity using Syrian hamster cells. None of these naturally occurring compounds induced sister chromatid exchanges and neither alpha-terthienyl nor phenylheptatriyne induced chromosome aberrations.

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Polyacetylenes and their thiophene derivatives were tested for their effects on human skin. Topically applied alpha-terthienyl evoked bi-phasic phototoxic dermatitis and the appearance of 'sunburn' cells in human epidermis. None of 11 polyacetylenes had the same effect although they mimicked alpha-terthienyl in their phototoxic effects on Candida albicans and certain pathogenic microorganisms. The UV-mediated antibiotic activity of the compounds and their apparent lack of phototoxicity towards the skin suggest a potential topical therapeutic role for them in yeast, fungal and bacterial infections and light-responsive dermatoses. Their topical sensitizing capacity, however, has not yet been studied.

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The tropical weed Bidens pilosa L. (Asteraceae) contains a number of polyacetylenes which are phototoxic to bacteria, fungi, and human fibroblast cells in the presence of sunlight, artificial sources of long-wave ultraviolet light, or cool-white fluorescent light. The principle photoactive compound in the leaf, phenylheptatriyne, is present in the cuticle as well as in the underlying cells. Experiments with calf thymus DNA indicate that, unlike photoactive furanocoumarins, phenylheptatriyne does not form interstrand cross linkages with DNA in ultraviolet light.

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A survey of North, Central, and South American composites, and of certain polyacetylenic compounds occurring in them, confirmed that the ultraviolet-mediated antibiotic activity against Candida albicans can be ascribed to the presence of particular polyacetylenes and their thiophene derivatives. Leaves, stems, roots, and achenes were assayed separately. An attempt was made to relate the phototoxic activity of specific compounds to their chemical structures. Most composites tested were not phototoxic against Candida, but many were antibiotic. The antibiotic activity also appears to be caused by polyacetylenes. Of 65 sequiterpene lactones assayed, only a few were found to be antibiotic, and only one, glaucolide G, was phototoxic.

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