Improved measurement of dibenzo[a,l]pyrene-induced abasic sites by the aldehyde-reactive probe assay.

Dibenzo[a,l]pyrene (DB[a,l]P) induces abundant amounts of depurinating adducts that spontaneously dissociate to form abasic sites in DNA. However, several previous studies that used the aldehyde-reactive probe (ARP) assay, could not verify abasic site formation by DB[a,l]P. Therefore, we examined whether a modification of the ARP assay would allow greater quantification of abasic sites.

Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate.

Senescence-associated changes in the prostate are believed to play an important role in the genesis of prostate cancer. In order to provide further information on how aging increases the prostate susceptibility to cancer, we examined the pattern of cyclooxygenase (COX)-2 expression and the concomitant alterations in prostaglandin E(2) (PGE(2)) synthesis in the prostate glands of 4-, 10-, 50- and 100-week-old Fischer 344 rats. This was carried out in the prostatic areas where hormone-induced tumors arise, namely the periurethral ducts of the dorsolateral prostate (DLP).

Inhibition of rat mammary gland carcinogenesis by simultaneous targeting of cyclooxygenase-2 and peroxisome proliferator-activated receptor gamma.

We examined the effect of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, and N-(9-fluorenyl-methyloxycarbonyl)-L-leucine (F-L-Leu), a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, separately and combined, on the development of methylnitrosourea (MNU)-induced rat mammary gland carcinogenesis. Celecoxib and F-L-Leu significantly reduced tumor incidence and multiplicity (P < 0.05).

Inhibition of cyclooxygenase-2 and activation of peroxisome proliferator-activated receptor-gamma synergistically induces apoptosis and inhibits growth of human breast cancer cells.

Cyclooxygenase-2 (COX-2) expression and peroxisome proliferator-activated receptor-gamma (PPARgamma) inactivation are linked to increased risk of human breast cancer. This study examines the effect of simultaneous targeting of COX-2 and PPARgamma on the proliferation of human breast cancer cells and on the expression of Bcl-2, BAX, and caspases-3 and -9, modulators of apoptotic cell death. Treatment of MDA-MB-231 breast cancer cells with NS-398 (a COX-2 inhibitor) or ciglitazone (CGZ, a PPARgamma-ligand) significantly inhibited cell proliferation and markedly increased apoptotic rates.

Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer.

Exposure to estrogens has been associated with an increased risk of developing breast cancer. Breast biopsy tissues from 49 women without breast cancer (controls) and 28 with breast carcinoma (cases) were analyzed by HPLC with electrochemical detection for 31 estrogen metabolites and catechol estrogen quinone-glutathione conjugates. The levels of estrone and estradiol were higher in cases.

Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma and levels of prostaglandin E2 and 15-deoxy-delta12,14-prostaglandin J2 in human breast cancer and metastasis.

Cyclooxygenase-2 (COX-2) expression and peroxisome proliferator-activated receptor-gamma (PPARgamma) inactivation are linked to increased risk of human breast cancer. The purpose of our study was to examine the relationship between COX-2 (with the resulting prostaglandins E(2), PGE(2)) and PPARgamma (and its natural endogenous ligand 15-Deoxy-Delta(12,14)-prostaglandin J(2), 15d-PGJ(2)) at various stages during the development of human breast cancer and its progression to metastasis. Human breast tissue specimens were collected from normal breasts or from individuals with fibrocystic disease and served as controls (n = 22).

DNA alkylation and repair in the large bowel: animal and human studies.

O6-methylguanine (O6-MeG), a procarcinogenic DNA adduct that arises from exposure to methylating agents, has been detected in human colorectal DNA at levels comparable to those that cause adverse effects in model systems. O6-MeG levels vary within the colon, being higher in the cancer-prone regions of the large bowel. In rats and mice, O6-MeG persistence in colon DNA is associated with the induction of colon tumors after treatment with methylating agents.

Influence of cigarette smoking on prostaglandin synthesis and cyclooxygenase-2 gene expression in human urinary bladder cancer.

The present study examines the effect of tobacco smoking on the expression of cyclooxygenase (COX)-2 gene, COX enzymatic activity and prostaglandin (PG) synthesis in urothelial mucosal tissues from patients with bladder cancer and from normal individuals. The detection frequency of COX-2 mRNA was 2-fold higher in bladder cancer patients compared to controls and it was accompanied by a significantly increased COX enzymatic activity and PGE2 synthesis (p < 0.05).

Cyclooxygenase-2 inhibitor celecoxib inhibits promotion of mammary tumorigenesis in rats fed a high fat diet rich in n-6 polyunsaturated fatty acids.

The objective of this investigation was to determine whether celecoxib, a highly specific inhibitor of cyclooxygenase-2 (COX-2), inhibits the promotion phase of mammary tumorigenesis in rats fed a high fat diet rich in n-6 polyunsaturated fatty acids (PUFAs) that is known to induce COX-2 expression. Sixty female Sprague-Dawley rats were initially maintained on an AIN-93G diet. At 50 days of age they received a single i.

Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma (Review).

Cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor-gamma (PPARgamma) have emerged as candidate molecules that hold great promise for cancer chemoprevention. COX-2 increased expression and PPARgamma inactivation occur during mammary gland carcinogenesis. COX-2 and PPARgamma may contribute to breast cancer induction either directly or via their effects on factors known to influence tumor development, e.

Catechol estrogen metabolites and conjugates in different regions of the prostate of Noble rats treated with 4-hydroxyestradiol: implications for estrogen-induced initiation of prostate cancer.

Prostate carcinomas arise in 100% of Noble rats treated with estradiol and testosterone. We hypothesize that estrogens initiate prostate cancer mainly by formation of 4-catechol estrogens (CE), followed by their oxidation to catechol estrogen-3,4-quinones (CE-3,4-Q), which can react with DNA. To avoid cancer initiation, CE can be detoxified by catechol-O-methyltransferase (COMT), and CE-3,4-Q by conjugation with glutathione (GSH) or by reduction to CE, catalyzed by quinone reductase and/or cytochrome P450 reductase.