Influence of an autocrine diffusible resistance factor on cell survival after exposure to therapeutic agents

Uk, Schlehaider; nd, Hill Gj; Hz, Hill

doi:10.1097/00008390-199310000-00010

Cited by 6 publications

(5 citation statements)

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“…leading to a high survival in relation to non-MDR cells (2,3). However, the MDR phenotype may be conferred by a number of other cellular alterations, such as mutation in the p53 gene (4), overexpression of MDR protein (MRP) (5) and production of a multitherapy resistance factor (6).…”

Section: Introductionmentioning

confidence: 99%

Differences in Sensitivity to UVC, UVB and UVA Radiation of a Multidrug‐Resistant Cell Line Overexpressing P‐Glycoprotein

Trindade

Capella

et al. 1999

Photochem & Photobiology

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Multidrug resistance (MDR) is the phenomenon in which cultured tumor cells, selected for resistance to one chemotherapeutic agent, simultaneously acquire resistance to several apparently unrelated drugs. The MDR phenotype is multifactorial. The best-studied mechanism involves the expression of a membrane protein that acts as an energy-dependent efflux pump, known as P-glycoprotein (Pgp), capable of extruding toxic materials from the cell. In this work, resistance to UVA radiation, but not to UVC nor UVB, was observed in an MDR leukemia cell line. This cell line overexpresses Pgp. To study the role of Pgp in the resistance to UVA radiation, two MDR modulators or reversing agents (verapamil and cyclosporin A) capable of blocking Pgp activity were used. Cell viability was assessed and the techniques of flow cytometry and fluorescence microscopy were employed to measure the extrusion of rhodamine 123 by the efflux pump. The results show that MDR modulators did not modify the resistance to UVA radiation. Furthermore, although cell viability was not significantly altered, Pgp function was impaired after UVA treatment, suggesting that this glycoprotein may be a physical target for oxidative damage, and that other factors may be responsible for the UVA resistance. In agreement with this, it was found that the resistant cell line presented a higher catalase activity than the parental (non-MDR) cell line.

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Section: Introductionmentioning

confidence: 99%

Differences in Sensitivity to UVC, UVB and UVA Radiation of a Multidrug‐Resistant Cell Line Overexpressing P‐Glycoprotein

Trindade

Capella

et al. 1999

Photochem & Photobiology

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“…No such studies were ever performed on the earlier genetically engineered cell lines. The results of these assays suggest that eumelanin pigment synthesized by tyrosinase alone, unmodified by the activities of the two tyrosinase related proteins TRP1 and TRP2 [Jackson et al, 1992;Hearing, 1993;Zhao et al, 1994;Kobayashi et al, 1995], is protective against the types of reactive oxygen species produced by UVA [Hill and Hill, 2000], ␥-rays [Hill, 1989;Hill et al, 1991] and, to some extent, UVB [Hill, 1989;Barker et al, 1995;Hill et al, 1997b;Hill and Hill, 2000] but sensitizes to UVC photons [Schlehaider et al, 1993]. UVC causes direct-effect damage and melanin adds to that some indirect-effect damage [Huselton and Hill, 1990;Menter et al, 1991;de Leeuw et al, 1995].…”

Section: Discussionmentioning

confidence: 99%

Transfection of nonmelanocytic cells with tyrosinase gene constructs for survival studies

Kaur

Hill

2001

Environ and Mol Mutagen

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To better understand the role of melanin in the response of cells to radiation, the vector pcTYR containing the tyrosinase cDNA and a control vector pcTYW with no tyrosinase cDNA were transfected and expressed in nonpigmented CHOK1-A(L) 1282B5 cells. A pigmented clone was selected from the pcTYR transfectants and an antibiotic-resistant clone was selected from the controls. Melanin was assessed qualitatively by electron paramagnetic resonance (EPR) and quantitatively by a 14C-based assay. The EPR signal detectable in pcTYR-containing cells was at least twice that of pcTYW and parental CHOK1-A(L) cells and the tyrosinase activity was found to be at least six times greater. Melanin was classified to be eumelanin. Survivals of the transfectants were compared to those of the parent cells after irradiation by UVC from a germicidal lamp, UVB from TL01 lamps, UVA from Alisun lamps, UVB/UVA from FS20 lamps, and by gamma-rays from a 137Cs source. Compared to the pcTYW-containing cells, the pigmented cells were more sensitive to killing by UVC, and resistant to killing by UVA and gamma-rays. There were no significant differences in survival after the other irradiations. These results suggest that the pigment synthesized by the activity of tyrosinase alone, unmodified by the activities of TRP1 and TRP2, is protective against the types of reactive oxygen species produced by UVA and gamma-rays but not protective against lethal damage from photons in the UVB range and sensitizes to UVC photons.

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“…In these Cloudman S91 melanoma cells, pigmentation is associated with increased induction of oxidative damage in DNA after irradiation with UVC (Huselton and Hill et al, 1990). S91/I3 cells are also more sensitive to killing by UVC-the SR is approximately 1.6 under conditions of maximum survival: killing of these cells by UVC is complicated by the fact that an autocrine factor produced most efficiently by S91/I3 is necessary for maximum survival of S9l/amel (Hill et al, 1992;Schlehaider et al, 1993). The factor does not affect of the two cell lines to the FS20 lamp put this assumption into question.…”

Section: Discussionmentioning

confidence: 99%

“…The cell lines used in these studies, S91A3 and SSlIamel, were the generous gift of Dr. John Pawelek, Department of Dermatology, Yale University, New Haven, CT Their growth, pigmentation, and responses to ionizing radiation and to UVC have been described previously (Orlow et al, 1990;Hill et al, 1991;Schlehaider et al, 1993;Cieszka et al, 1995). They are routinely maintained in RPMI1640 medium supplemented with 5% fetal bovine serum (RPMI5).…”

Section: Materials and Methods Cellsmentioning

confidence: 99%

“…No such damage occurred at comparable doses in a non-melanoma cell line. S91/13 cells are also more sensitive to killing by UVC than S9l/amel (Schlehaider et al, 1993). This greater sensitivity to the lethal effects of UVC of S91A3 suggests that oxidative damage in DNA is enhanced in these cells by the additional pigment and that such damage under some circumstances may have clinical relevance.…”

Section: Introductionmentioning

confidence: 99%

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Survival of Cloudman Mouse Melanoma Cells After Irradiation by Solar Wavelengths of Light

Cieszka

Hill

Xin

et al. 1997

Pigment Cell Research

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A number of variants of Cloudman S91 mouse melanoma cells that differ with respect to the amount of pigment produced are available for study. In this report, we compare the photobiological responses of S91/amel, which contains about 1 pg of melanin per cell, with S91/I3, which contains about 3 pg/cell. Earlier studies had shown that UVC induced more oxidative damage (in the form of thymine glycols) in cell line S91/I3 than in S91/amel and that cell line S91/amel was more resistant to killing by UVC than S91/I3. The present study finds that S91/amel cells are also relatively resistant to killing by near monochromatic UVB from a Philips TL01 fluorescent lamp and by near monochromatic UVA from a Philips HPW125 lamp. However, when the cells are irradiated with a Westinghouse FS20 polychromatic lamp, the S91/I3 cells are more resistant than the S91/amel cells. These findings cannot be explained on the basis of pigment induction because in S91/I3 this is about the same after UVB and FS20, although the maximum is reached earlier after UVB. Nor can our findings be explained on the basis of pyrimidine dimer formation, which is comparable in the two cell lines regardless of the type of irradiation. These results suggest that, with a pigment such as melanin, which absorbs light across the visible and ultraviolet ranges of the spectrum, cellular responses to monochromatic light do not necessarily predict responses to polychromatic mixtures.

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Influence of an autocrine diffusible resistance factor on cell survival after exposure to therapeutic agents

Cited by 6 publications

References 0 publications

Differences in Sensitivity to UVC, UVB and UVA Radiation of a Multidrug‐Resistant Cell Line Overexpressing P‐Glycoprotein

Differences in Sensitivity to UVC, UVB and UVA Radiation of a Multidrug‐Resistant Cell Line Overexpressing P‐Glycoprotein

Transfection of nonmelanocytic cells with tyrosinase gene constructs for survival studies

Survival of Cloudman Mouse Melanoma Cells After Irradiation by Solar Wavelengths of Light

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