Cell-transforming activity and genotoxicity of phenolphthalein in cultured Syrian hamster embryo cells.
Phenolphthalein is a cathartic agent widely used in non-prescription laxatives. For the simultaneous assessment of in vitro carcinogenicity and mutagenicity of phenolphthalein, the ability of this chemical to induce cell transformation and genetic effects was examined using the Syrian hamster embryo (SHE) cell model. Cell growth was reduced by treatment with phenolphthalein at 10-40 microM in a dose-related manner. Treatment with phenolphthalein for 48 hr induced a dose-dependent increase in morphological transformation of SHE cells. Over the dose range that resulted in cell transformation ( 10-40 microM), treatment of SHE cells with phenolphthalein induced gene mutations at the hprt locus but not at the Na+/K+ ATPase locus. A statistically significant level of chromosomal aberrations was elicited in SHE cells treated with phenolphthalein at the highest dose (40 microM). Meanwhile, neither numerical chromosomal changes nor DNA adduct formation, analyzed by the nuclease P1 enhancement version of 32P-post-labeling, were induced by treatment with phenolphthalein at any concentrations examined. We thus report cell-transforming activity and mutagenicity of phenolphthalein assessed with the same mammalian cells in culture. Our results provide evidence that phenolphthalein has cell-transforming and genotoxic activity in cultured mammalian cells. The mutagenic and clastogenic activities of phenolphthalein could be a causal mechanism for carcinogenicity in rodents.
Tsutsui
T
T
Department of Pharmacology, The Nippon Dental University, Tokyo, Japan.
Tamura
Y
Y
Yagi
E
E
Hasegawa
K
K
Tanaka
Y
Y
Uehama
A
A
Someya
T
T
Hamaguchi
F
F
Yamamoto
H
H
Barrett
J C
JC
D000818:Animals; D002400:Cathartics / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D018736:DNA Adducts / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000187:drug effects / Q000235:genetics; D008647:Mesocricetus / Q000196:embryology*; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D020113:Phenolphthalein; D010635:Phenolphthaleins / Q000737:chemistry / Q000633:toxicity*
D002400:Cathartics; D018736:DNA Adducts; D010635:Phenolphthaleins; D020113:Phenolphthalein; D007041:Hypoxanthine Phosphoribosyltransferase