Screening for BRCA1 large genomic rearrangements in female Egyptian hereditary breast cancer patients.

Approximately 5%-10% of all breast cancers are inherited as the result of germline mutations in the BRCAl gene. Large genomic rearrangements (LGRs) in BRCA1 have not been well-researched in the Egyptian population. Using multiplex ligation-dependent probe amplification, we showed BRCA1 rearrangements in 4/22 cases (18.2%) of familial breast cancer. No influence of having multiple breast cancer cases within the family was observed in patients diagnosed at or=45 years and having BRCAl-positive LGRs. However, focusing on cases with first- and second-degree relatives affected, we observed a significant difference between the percentage of patients with BRCA1-positive versus BRCAl-negative LGRs. Our results provide the first evidence that LGRs in BRCA1 exist in the Egyptian population. Screening for these alterations may be desirable when breast cancer patients are diagnosed at an early age, especially if these cases have first- and second-degree of relatives with breast cancer.

Prevention of skin tumors induced by 7,12-dimethylbenz(a)anthracene in mice by black seed oil.

The effect of topical application of black seed oil on 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin tumors in BALB/c mice was investigated. Topical application of chemically extracted oil (C.O.) and naturally extracted oil (N.O.) highly prevented the appearance of skin tumors in experimental animals. Skin tumors (papillomas and carcinomas) were initiated by application of 300 mu g DMBA (on days 1,8) followed by applying 0.5 mg croton oil, biweekly until the end of the experiment (25 weeks). The application of N.O. completely prevented the appearance of skin tumors in mice of group 3 versus a tumor incidence of 78.9% in animals of group 1 (carcinogenic control) (cc). Painting the skin of mice with C.O. (group 2) significantly reduced the tumor incidence to 14.2%. Moreover, a significant decrease was observed in number of mice bearing tumors, and number of tumors per mouse in group 2. Multiplicity was also decreased but insignificantly in the same group. The treatment with C.O. and N.O. insignificantly increased the rate of mice survival as compared to that of animals of group 1.

Inflammatory effects of the tumor promoter croton-oil in BALB/c mice skin.

A single dose of 0.25% croton oil induced an edema when applied to the ears of BALB/c mice. The maximal edematous response resulted from a single application of 4% croton oil. At any dose level, edema maximized 6-7 h after croton oil application, waning thereafter to the control level by 30 h. When topically applied on the shaved back skin, a single dose of 0.25% croton oil induced an inflammatory effect characterized by epidermal hyperplasia and infiltration of polymorphonuclear leucocytes (PMNs) in the dermis. Higher doses of croton oil caused more remarkable inflammatory response. The histological changes which were slightly detected in the skin 4 h after application of croton oil, reached a maximal level by 20-27 h, but substantially subsided by 72 h. Results proved that the tumor-promoter croton oil induces an inflammation in mice skin in a dose- and time-dependent process.

Inhibition of mammary-gland tumorigenesis in the rat by caraway seeds and dried leaves of watercress.

The effect of consumption of caraway seeds and dried leaves of watercress on 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats was determined. At 6 weeks of age, animals were fed a basal (control) diet and experimental diets containing caraway or watercress (20%). Animals were maintained on their diets till termination of the experiment (25 weeks after DMBA). At 8 weeks of age, all rats were given DMBA 10 mg, one dose, p.o. in oily formulation). Neither caraway nor watercress affected the body weight or the rate of growth of animals. By week 25 after DMBA, 77% of the control rats developed mammary tumors, with a mean of 2.27 tumors per rat. Caraway decreased significantly (P<0.05) the percentage of rats with tumors (42.8% protection) and the mean number of tumors per rat (50.6% protection) and increased significantly (P<0.05) the mean latency period of tumor appearance. Watercress, though decreased the percentage of rats with tumors (28.5% protection) and the mean number of tumors per rat (31.7% protection), this decrease was significant (P < 0.05) during some week intervals only. The increase in the mean latency period of tumor appearance by watercress was not significant. The results of this study suggest that caraway and watercress possess chemopreventive effects against DMBA-induced mammary gland tumorigenesis in rats.

Induction of breast neoplasia and lung granulomas in mice by an antifungal drug (griseofulvin).

Infiltrating duct carcinomas were induced in the mammary glands of 7 out of 60 experimental female mice force-fed with the antifungal drug griseofulvin, at a daily dose lever of 0.3 mg/30g body weight, for 12 months. The first mammary gland tumor appeared 8 months after the initiation of feeding. Other pathological changes such as bronchocentric granulomas appeared in some male and female treated animals (16.5%).

Caraway oil inhibits skin tumors in female BALB/c mice.

Caraway oil, supplemented in diet or painted on the skin, inhibited 7,12-dimethylbenz[a]anthracene- (DMBA) and croton oil-induced skin tumors in female BALB/c mice. The inhibition was manifested by disappearance of carcinomas, reduced incidence and number of papillomas, delay of their appearance, retardation of their development, and regression of already established papillomas. Caraway oil is more effective when topically applied than when supplemented in the diet.

Carcinogenic effect of force-feeding an extract of black pepper (Piper nigrum) in Egyptian toads (Bufo regularis).

50 male and 50 female Bufo regularis were treated, by force-feeding, with an extract of black pepper, at a dose level of 2 mg, 3 times a week for 5 months. The first tumors appeared after 2 months. Liver tumors (hepatocellular carcinomas, lymphosarcomas and fibrosarcomas) were found in 12 males and 18 females. Metastatic deposits of hepatocellular carcinomas were registered in the spleen, kidney, fat body and ovary.

Carcinogenesis induced by black pepper (Piper nigrum) and modulated by vitamin A.

Painting and feeding of mice with 2mg of an extract from black pepper on 3 days a week for 3 months results in a significant increase of the number of tumor-bearing mice. Tumor incidence is reduced in those groups of experimental animals receiving 5 or 10mg Vitamin A-palmitate twice weekly for 3 months by feeding or painting during and subsequent to application of pepper extract. Feeding of mice with powder of black pepper in diet (50g/3kg food) has no impact on carcinogenesis.

Carcinogenicity testing of black pepper (Piper nigrum) using the Egyptian toad (Bufo regularis) as a quick biological test animal.

Milled black pepper (Piper nigrum) force-fed to Egyptian toads as a suspension in amphibian saline or injected subcutaneously in the dorsal lymph sac as an ethanol extract, induced primary tumours in the liver and secondary tumours in other organs (kidney and spleen). When applied to the skin of experimental animals as an ethanol extract, black pepper induced primary tumours in the liver and secondary tumours in the ileum and stomach. Tumours of the liver were diagnosed as hepatocellular carcinomas and those of the other organs as metastases of the primary liver tumours. It is speculated that one or more constituents of black pepper may be responsible for tumour induction in the organs of the Egyptian toad Bufo regularis.