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Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on murine skin
1Department of Medicine, UCLA School of Medicine 90024.
Abstract:
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on skin of congenic haired and hairless newborn and adult HRS/J mice was studied. In all adult animals topical application of TCDD caused an involution of sebaceous glands. Epidermal/epithelial hyperplasia and hyperkeratinization was induced in the hairless, but not the haired mice. Trans-glutaminase (TG) activity was stimulated in both haired and hairless animals. A single application of 1 microgram of TCDD did not stimulate significant ornithine decarboxylase activity in the skin in either strain. Other than a reduction in the density of the inflammatory cell infiltrate in the dermis, topical treatment with antiinflammatory agents fluocinolone acetonide and indomethacin did not affect the cutaneous response to TCDD. Skin of newborn mice treated topically with TCDD over a 2-wk period reacted much the same as adult skin in that sebaceous glands were reduced in size and TG activity was stimulated in both haired and hairless neonates; but epidermal hyperplasia occurred only in the hairless, not the haired newborns.
Insights
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects mouse skin by reducing sebaceous glands and stimulating trans-glutaminase activity. Epidermal hyperplasia occurred only in hairless mice, regardless of age.
Area of Science:
- Toxicology
- Dermatology
- Biochemistry
Background:
- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxicant.
- The skin is a target organ for TCDD toxicity.
- Congenic haired and hairless HRS/J mice provide a model to study genetic influences on TCDD-induced skin effects.
Purpose of the Study:
- To investigate the effects of TCDD on the skin of haired and hairless mice.
- To compare the responses in newborn and adult animals.
- To examine the role of trans-glutaminase (TG) and ornithine decarboxylase (ODC) activity.
Main Methods:
- Topical application of TCDD to haired and hairless HRS/J mice (newborn and adult).
- Assessment of sebaceous gland size, epidermal hyperplasia, hyperkeratinization, and TG activity.
- Measurement of ODC activity.
- Evaluation of anti-inflammatory agents' effects.
Main Results:
- TCDD caused sebaceous gland involution in all adult mice.
- Epidermal hyperplasia and hyperkeratinization were observed in hairless mice but not haired mice.
- Trans-glutaminase (TG) activity was stimulated in both haired and hairless mice.
- Newborn mice showed similar responses to adults, with hyperplasia only in hairless neonates.
- Anti-inflammatory agents did not significantly alter the cutaneous response to TCDD.
Conclusions:
- TCDD induces distinct cutaneous responses in haired and hairless mice.
- Age and hair presence influence TCDD's effect on epidermal hyperplasia.
- TG activity is a sensitive indicator of TCDD exposure in mouse skin.
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