Sister chromatid exchanges and chromosome aberrations in lymphocytes of medical personnel handling cytostatic drugs.

Many anticancer drugs, including cytostatic drugs, are genotoxic. Evidence on human carcinogenicity has been conclusive. Persons handling these drugs might be exposed to an occupational health hazard, as they cause chromosomal damage in the lymphocytes. This study was conducted on 30 Egyptian medical personnel handling cytostatic drugs, working in the Medical Research Institute, Alexandria University and Gamal Abd El Naser Hospital in Alexandria. A control group comprised 30 normal healthy individuals matched for age and sex and had no contact with cytostatic drugs. Also, they were not exposed to any mutagenic agents. The workers and controls were interviewed to exclude exposure to any mutagenic agents other than anticancer drugs in case of medical workers. Cytogenetic methods were done to all subjects to assess chromosomal aberrations (CA) and sister chromatid exchanges (SCE). Significantly increased frequencies of CA and SCEs were found in exposed personnel as compared to the controls. Chromosomal aberrations and SCEs frequencies were not correlated with the age of exposed personnel and duration of exposures to cytostatic drugs. There was no increased risk of malformed children in exposed females and no history of repeated abortion. The results of this study point to the handling of cytostatic drugs as a possible genotoxic hazard. Therefore, effective protection and care in handling must be further emphasized to prevent adverse effects.

Familial male breast cancer. A case report and review of the literature.

The occurrence of breast cancer in aged male and his paternal uncle is reported. A review of previously reported cases of male breast cancer (M.B.C.) occurring in families and the association with other cancers in the family members is included. Familial or hereditary factors have not been recognized as a major contributing factor in previous reports. Seven families (63.6%) out of eleven families reported had females with breast cancer. It appears that there are some families in which males as well as females have increased risk of developing breast cancer. It is believed that this report supports the genetic predisposition of breast cancer in males. Estrogen affects the growth of breast cancer through estrogen receptor. An approach to subsequent genetic studies of breast cancer may be to focus on steroid hormone receptors.

Effect of dextran-coated charcoal treatment on 17 beta-estradiol receptor in human benign prostatic hyperplasia.

Using glycerol density gradient centrifugation technique, single saturation dose assay, and Scatchard plot, the effect of dextran-coated charcoal (DCC) treatment of homogenate or crude cytosol on estradiol binding protein in human benign prostatic hyperplasia was investigated. Receptor binding is increased after thirty minutes DCC treatment of homogenate or cytosol. Increase in estradiol binding is accompanied by loss in cytosolic protein. A 75 per cent increase in binding of estradiol to its receptor was observed after two hours incubation of DCC with homogenate. The concomitant increase in estradiol binding and decrease in protein concentration in both homogenate or cytosol after DCC treatment indicate the possible removal of some protein(s) which inactivate(s) the estradiol receptor. Removal of cofactors required for activation of proteases and removal of endogenous steroids which could be occupying the estradiol sites also are possible. This simple experimental procedure has improved significantly the methodology for the measurement and characterization of estrogen receptor in human BPH.

A multifactorial analysis of steroid hormone receptors in stages I and II breast cancer.

It has been shown that the level of estrogen receptors (ER), and to some extent progesterone receptors (PR), correlate to a high degree to the response to endocrine therapy in advanced breast cancer patients. To evaluate the prognostic value of ER/PR in early breast cancer, 80 patients with stages I and II were studied. They all underwent modified radical mastectomy. Patients with stage I disease (negative LN) received no further treatment, while those with stage II received standard adjuvant chemotherapy. All the patients were followed for 4 years. The ER and PR were measured in each primary tumor by the glycerol density gradient method. Values of 10 fmole/mgm protein or greater were considered positive (+) and less than 10 fmole/mgm were considered negative (-). The results revealed: (1) Fifty-two patients (65%) had ER+, of which 44 (85%) were also PR+; 28 patients had ER-, of which 24 were also PR- (p less than 0.0001). (2) ER/PR correlated with age as 71% of the patients over age 50 had ER+/PR+, compared to 33% of those under age 50 (p less than 0.05). (3) Postmenopausal patients had a higher incidence of ER+/PR+. (4) Primary tumors less than 2 cm in size had higher ER+; 71% in those with stage I and 80% in stage II. (5) Fifty-eight per cent (38) of patients with ductal carcinoma had ER+/PR+, compared to 67% (4) with lobular carcinoma. (6) The disease-free survival of patients with ER+ tumors was significantly longer than those with ER- tumors (p less than 0.005) both in positive and negative LN patients. The same was true for PR+ compared to PR- (p less than 0.005), but only in those with stage II disease. The overall survival rates were similarly significant in favor of ER+ and PR+ patients (p less than 0.025), but only in stage II disease. It seems that the status of steroid hormone receptors has a major prognostic factor second only to the LN status.