Primary DNA damage, HPRT mutation and cell inactivation photoinduced with various sensitizers in V79 cells.

Abstract

DNA strand breaks and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutants were measured in parallel in photochemically treated (PCT) cells and compared at the same level of cell survival. Chinese hamster fibroblasts (V79 cells) were either incubated with the lipophilic dyes tetra(3-hydroxyphenyl)porphyrin (3THPP) and Photofrin II (PII), the anionic dye meso-tetra(4-sulfonatophenyl)porphine (TPPS4) or the cationic dye meso-tetra(N-methyl-4-pyridyl)porphine (p-TMPyPH2) before light exposure. In the cells, the lipophilic dyes were localized in membranes, including the nuclear membrane, while the hydrophilic dyes were taken up primarily into spots in the cytoplasm. In addition, the hydrophilic TPPS4 was distributed homogeneously throughout the whole cytoplasm and nucleoplasm. According to the HPRT mutation test, the mutagenicity of light doses survived by 10% of the cells was a factor of six higher in the presence of 3THPP than of PII, whereas for X-rays it was a factor of three higher than for PCT with 3THPP. Light exposure in the presence of the hydrophilic dyes TPPS4 and p-TMPyPH2 was not significantly mutagenic. There was no correlation between the induced rates of HPRT mutants and of DNA strand breaks. Thus, TPPS4 was the most efficient sensitizer with regard to DNA strand breaks when compared at the same level of cell survival, followed by 3THPP, PII and p-TMPyPH2. Hence, the rate of DNA strand breaks cannot be used to predict the mutagenicity of PCT.