Acute treatment with kerosene damages the dermal barrier and alters the distribution of topically applied benzo(a)pyrene in mice.

The dermal route is important in many occupational exposures. Some materials may reduce the barrier function of the skin to enhance absorption and effect on internal organs. We have reported previously that kerosene cleaning following treatment with used engine oil increased DNA adduct levels in the lungs of mice compared with animals treated with used oil alone.

Gene expression profiling of blood to predict the onset of leukemia.

No studies have tested the hypothesis that the onset of a disease can be predicted by gene expression profiling. The AKR/J mouse strain, which spontaneously develops acute T cell lymphatic leukemia, was used to implement a novel strategy to generate global gene expression profiles of WBCs at different time points. The experimental approach was bias free because it was unknown as to which individuals in the mouse population would eventually develop the disease.

Enhanced degradation of benzo[a]pyrene by Mycobacterium sp. in conjunction with green alga.

Previous work in this laboratory has confirmed that the bacteria Mycobacterium sp. strain RJGII.135 and Sphingomonas yanoikuyae strain B1 and the green alga Selanastrum capricornutum strain UTEX 1648 degrade benzo[a]pyrene (BaP) to various BaP intermediates.

Impact of Cyp1a2 or Ahr gene knockout in mice: implications for biomonitoring studies.

Unlabelled: Studies of the impact of phase 1 enzyme polymorphisms on genetic damage have yielded mixed results. We studied how genetic damage would be altered when specific genes were ablated under low dose conditions.

Methods: Knockouts (KO) were generated from c57bl6/J mice with mutations in Cyp1a2 or Ahr receptor that eliminated gene product function.

Expression of angiogenic factors is upregulated in DMBA-induced rat mammary pathologies.

Objective: In the 7,12-dimethylbenz[a]anthracene (DMBA) model of rat mammary carcinogenesis, microvascular density and angiogenic potential increase with progression from normal to invasive disease, but the mechanisms involved are unknown. Using RT-PCR, we determined the expression of angiogenic regulators in DMBA-induced intraductal hyperplasia (IDP), carcinoma in situ (CIS), invasive tumors (INV), as well as normal tissue.

Methods: RT-PCR was performed on frozen tissue sections of each type of pathology for factors known to regulate angiogenesis in other systems.

Inhibition of VEGFR2 prevents DMBA-induced mammary tumor formation.

Preinvasive mammary pathologies in humans and rat chemical carcinogenesis model systems have an increased microvascular density relative to normal tissue. This suggests the possibility of preventing invasive breast cancer by inhibiting angiogenesis. Vascular endothelial cell growth factor (VEGF) is a potent angiogenic growth factor, commonly involved in tumor-induced angiogenesis.

TNP-470 inhibits 7,12-dimethylbenz[a]anthracene-induced mammary tumor formation when administered before the formation of carcinoma in situ but is not additive with tamoxifen.

In many women pathologic lesions, such as hyperplasia and carcinoma in situ, precede invasive breast cancer. We have shown that tissue vascularity increases with histologic progression to invasive disease. Similarly, in the well-characterized 7,12-dimethylbenz[a]anthracene (DMBA) model of mammary tumorigenesis, preinvasive lesions exhibit increased vascularity with progression.

Reduction of a 7,12-dimethylbenz[a]anthracene DNA adduct in rat mammary tissue in vivo when pretreated with tamoxifen.

Tamoxifen (TAM), an antiestrogenic compound, has been approved for the treatment of breast cancer in high risk women. TAM has been shown to be an effective agent for prevention of breast cancer in women of varying degrees of risk and has been proposed to be used prophylactically in women whose genetic background suggests a high risk for breast cancer. However, it is not known whether TAM given prophylactically will alter the response of women to carcinogens from common environmental exposures such as tobacco smoke.