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Much of the work carried out by DTT is in support of the National Toxicology Program (NTP), an interagency partnership of the Food and Drug Administration, National Institute for Occupational Safety and Health, and NIEHS.

Molecular Pathogenesis Group

Endometrial cancer accounts for approximately 7% of all invasive cancers in U.S. women with the exception of skin cancer. This type of uterine cancer usually affects postmenopausal women aged 55-65 years. There is evidence which suggests that these tumors are caused or influenced by prolonged estrogen stimulation. In B6C3F1 mice, endometrial cancer can be induced by haloalkanes. We are using this in vivo system as a model for studying chemically or environmentally induced endometrial cancer.

Bromoethane, chloroethane and ethylene oxide are mutagenic alkylating agents. Bromoethane is a chemical in the class of halogenated alkanes, which encompasses a wide range of industrial and pharmaceutical agents. Haloalkanes are highly lipophilic and readily cross the blood-brain barrier. Bromoethane has limited commercial use as an ethylating agent in organic syntheses, for ethylation of gasoline, and has been formerly used as an anesthetic. To a much lesser extent it was formerly used as a fruit and grain fumigant, refrigerant, and a solvent. Bromoethane occurs naturally and is formed by marine algae.

The mechanism by which bromoethane, chloroethane or ethylene oxide cause uterine tumors following inhalation exposure is not clear. Most of the mechanistic studies assessing the induction of endometrial tumors with these chemicals have been done with chloroethane. It has been suggested that the specificity for chloroethane to cause uterine tumors in mice may depend on the species-specific metabolism of chloroethane in mice.