title: Lack of promoting effect of titanium dioxide particles on ultraviolet B-initiated skin carcinogenesis in rats.
abstract: Titanium dioxide (TiO(2)) is used in sunscreens and cosmetics as an ultraviolet light screen. TiO(2) has carcinogenic activity in the rat lung, but its effect on the skin has not been reported. We examined the promoting/carcinogenic effect of nano-size TiO(2) particles using a two-stage skin model. c-Ha-ras proto-oncogene transgenic (Hras128) rats, which are sensitive to skin carcinogenesis, and their wild-type siblings were exposed to ultraviolet B radiation on shaved back skin twice weekly for 10 weeks; then the shaved area was painted with a 100 mg/ml TiO(2) suspension twice weekly until sacrifice. All rats were killed at week 52 except for female Hras128 rats which were sacrificed at week 16 because of early mammary tumor development. Skin tumors developed in male Hras128 rats and mammary tumors developed in both sexes of Hras128 rats and in wild-type female rats, but tumor incidence was not different from controls. TiO(2) particles were detected in the upper stratum corneum but not in the underlying skin tissue layers. TiO(2) particles also did not penetrate a human epidermis model in vitro. Our data suggest that TiO(2) does not cause skin carcinogenesis, probably due to its inability to penetrate through the epidermis and reach underlying skin structures.
authors.affiliation: Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Jiegou
authors.initials: J
authors.lastname: Xu
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sagawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Futakuchi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fukamachi
authors.forename: David B
authors.initials: DB
authors.lastname: Alexander
authors.forename: Fumio
authors.initials: F
authors.lastname: Furukawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uchino
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Nishimura
authors.forename: Akimichi
authors.initials: A
authors.lastname: Morita
authors.forename: Masumi
authors.initials: M
authors.lastname: Suzui
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D053758:Nanoparticles; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000090063:Proto-Oncogene Mas; D051381:Rats; D055647:Rats, Transgenic; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012869:Skin Absorption; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013473:Sunscreening Agents / Q000378:metabolism / Q000633:toxicity*; D014025:Titanium / Q000378:metabolism / Q000633:toxicity*; D014466:Ultraviolet Rays
chemical_list: D002273:Carcinogens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013473:Sunscreening Agents; C009495:titanium dioxide; D014025:Titanium