Skin tumor-promoting potential and systemic effects of pentachlorophenol and its major metabolite tetrachlorohydroquinone in CD-1 Mice.
The mouse skin carcinogenesis model provides a conceptual framework to study the carcinogenesis process. It has been used extensively to assess whether a chemical or physical agent carries a carcinogenic hazard to humans and to define the mechanism involved with the carcinogenic effects. We conducted a study to evaluate whether the tumor-promoting activity of pentachlorophenol (PCP) is mainly from its major metabolite tetrachlorohydroquinone (TCHQ). We applied the mouse skin model to CD-1 mice and the results showed that PCP and TCHQ are much weaker promoters than 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin during a 25-wk experiment. Both PCP and TCHQ could induce mice skin epidermal hyperplasia and proliferating cell nuclear antigen (PCNA) labeling index in the epidermis. However, TCHQ caused a more significant induction of epidermal hyperplasia and PCNA positive cells than PCP. Topical application of PCP, but not TCHQ, induced significant organ enlargement and lymphoma in mice, whereas short-term treatment of TCHQ increased tumor necrosis factor-alpha (TNF-alpha) gene expression in mouse skin. We did not observe a significant association between the carcinogenic process and serum TNF-alpha or interleukin-1 beta (IL-1 beta) levels in mice.
Chang
Wen-Ching
WC
Graduate Institute of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Jeng
Jiiang-Huei
JH
Shieh
Chi-Chang
CC
Tsai
Yi-Chang
YC
Ho
Yuan-Soon
YS
Guo
How-Ran
HR
Liu
Hsin-I
HI
Lee
Ching-Chang
CC
Ho
Sheng-Yow
SY
Wang
Ying-Jan
YJ
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000287:Administration, Topical; D000818:Animals; D002273:Carcinogens; D005260:Female; D006965:Hyperplasia; D007375:Interleukin-1 / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D010416:Pentachlorophenol / Q000493:pharmacokinetics / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D012878:Skin Neoplasms / Q000139:chemically induced*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D002273:Carcinogens; D007375:Interleukin-1; D018809:Proliferating Cell Nuclear Antigen; D014409:Tumor Necrosis Factor-alpha; D015127:9,10-Dimethyl-1,2-benzanthracene; D010416:Pentachlorophenol