In 1996 we continued to examined the effects of ethylene glycol monmeethyl ether (EGME) on ovarian function. To better predict potential human health risks, we examined the effects of the proximate metabolite of EGME, 2-methoxy acetic acid or MAA, on primary cultures of human luteal cells. We found that the human luteal cell response to MAA is quite comparable to the rat luteal cell response in vitro, and predicit this data will be used to help determine acceptable exposure limits in women. We have also described the development of ovarian tumors in adult female Sprague-Dawley rats exposed to TCDD (dioxin) and are currently determining the tumor morphology and origin, and determining whether the ovary and these tumors have the Ah receptor. We also continued to examine the in situ expression of BRCA1 in the mouse ovary and have demonstrated that BRCA1 expression is independent of hormonal stimulation, but is dependent on the cell cycle. We are also developing probes for in situ hybridization studies of BRCA1 in the rat, and BRCA2 in the mouse and the rat. Finally, we are defining the role of cyclooxygenase 1 and cycloxygenase 2 (COX 1 and COX 2) in the ovary using the mice defecient in these enzymes and have established that COX2 is necessary for ovulation induction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021197-03
Application #
2574291
Study Section
Special Emphasis Panel (LEP)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Pritchard, John B; French, John E; Davis, Barbara J et al. (2003) The role of transgenic mouse models in carcinogen identification. Environ Health Perspect 111:444-54
Lovekamp-Swan, Tara; Jetten, Anton M; Davis, Barbara J (2003) Dual activation of PPARalpha and PPARgamma by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells. Mol Cell Endocrinol 201:133-41
McAllister, Kimberly A; Bennett, L Michelle; Houle, Chris D et al. (2002) Cancer susceptibility of mice with a homozygous deletion in the COOH-terminal domain of the Brca2 gene. Cancer Res 62:990-4
Houle, Christopher D; Ding, Xiao-Yu; Foley, Julie F et al. (2002) Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression. Gynecol Oncol 86:69-78
Bennett, L Michelle; Davis, Barbara J (2002) Identification of mammary carcinogens in rodent bioassays. Environ Mol Mutagen 39:150-7
Hoppin, Jane A; Brock, John W; Davis, Barbara J et al. (2002) Reproducibility of urinary phthalate metabolites in first morning urine samples. Environ Health Perspect 110:515-8
Davis, B J; Price, H C; O'Connor, R W et al. (2001) Mercury vapor and female reproductive toxicity. Toxicol Sci 59:291-6
Davis, B J; Travlos, G; McShane, T (2001) Reproductive endocrinology and toxicological pathology over the life span of the female rodent. Toxicol Pathol 29:77-83
Bennett, L M; McAllister, K A; Ward, T et al. (2001) Mammary tumor induction and premature ovarian failure in ApcMin mice are not enhanced by Brca2 deficiency. Toxicol Pathol 29:117-25
Lovekamp, T N; Davis, B J (2001) Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and estradiol production in cultured rat granulosa cells. Toxicol Appl Pharmacol 172:217-24

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