Cycloheximide-dependent reversion of human cells transformed by MSV and chemical carcinogen

The induction of rat mammary carcinoma by the chemical carcinogen DMBA is used as a model for the study of the human disease (1). We previously described the histochemical changes that occur in the mammary gland of DMBA treated animals before the earliest manifested histological change, the intraductal proliferation (IDP), was observed (2). In the present work, we demonstrate that a change in the stable cell population found in the resting mammary gland occurs after carcinogen administration.Fifty-five day old Sprague-Dawley virgin female rats were inoculated intragastrically with 20mg of 7,12-dimethylbenz(a)anthracene (DMBA) in 1ml sesame oil. Non-inoculated, age-matched females were used as controls. Mammary glands from control and inoculated rats were removed weekly from the time of inoculation until 60 days post-inoculation. For electron microscopy, the glands were immersed in Karnovsky's fixative, post-fixed in 1% OsO4, dehydrated, and embedded in an Epon-Araldite mixture. Thick (lμ) sections were stained with 1% toluidine blue and were used for selecting areas for ultrastructural study.

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Alpha-Tocopherol Protects Cultured Human Cells from the Acute Lethal Cytotoxicity of Dioxin

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.72.3.147 ◽

2002 ◽

Vol 72 (3) ◽

pp. 147-153 ◽

Cited By ~ 8

Author(s):

Kei-Ichi Hirai ◽

Jie-Hong Pan ◽

Ying-Bo Shui ◽

Eriko Simamura ◽

Hiroki Shimada ◽

...

Keyword(s):

Cell Death ◽

Cell Damage ◽

Smooth Endoplasmic Reticulum ◽

Dehydroascorbic Acid ◽

Human Cells ◽

Alpha Tocopherol ◽

Cervical Cancer Cells ◽

Cultured Human Cells ◽

Nuclear Damage ◽

Conjunctival Epithelial Cells

The possible protection of cultured human cells from acute dioxin injury by antioxidants was investigated. The most potent dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), caused vacuolization of the smooth endoplasmic reticulum and Golgi apparatus in cultured human conjunctival epithelial cells and cervical cancer cells. Subsequent nuclear damage included a deep irregular indentation resulting in cell death. A dosage of 30–40 ng/mL TCDD induced maximal intracellular production of H2O2 at 30 minutes and led to severe cell death (0–31% survival) at two hours. A dose of 1.7 mM alpha-tocopherol or 1 mM L-dehydroascorbic acid significantly protected human cells against acute TCDD injuries (78–97% survivals), but vitamin C did not provide this protection. These results indicate that accidental exposure to fatal doses of TCDD causes cytoplasmic free radical production within the smooth endoplasmic reticular systems, resulting in severe cytotoxicity, and that vitamin E and dehydroascorbic acid can protect against TCDD-induced cell damage.

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