The cytoplasmic receptors for 17fl-estradiol (ER), 5a-dihydrotestosterone (AR), progesterone (PR), and cortisol (GR) have been quantified in 36 specimens from the human ovary (13 disease-free, 5 benign, and 18 malignant) by a dextran-coated charcoal (DCC) technique. The occurrence of receptor-positive biopsies were: ER 46%, AR 85%, PR 54%, GR 92%, in normal tissue; ER 40%, AR loo%, PR 20%, GR SO%, in benign tumors; and ER 67%, AR 72%, PR SO%, GR 88%, in malignant lesions. Furthermore, the simultaneous occurrence of ER and PR in malignant tumors was 50% yet all four receptors were found to be present only in 44% of the cases. The findings reported here on the strong correlation existing between ER and PR presence or amount agree with previous observations on normal and neoplastic specimens from human breast and endometrial tissues.

The cytoplasmic concentrations of ER, AR, PR, and GR were determined in 124 specimens of normal and abnormal endometrium and other uterine human tissues by the DCC technique. In the endometrial carcinoma group, we observed that pretreatment with MAP leads to low cellularity, higher amount of AR, lower amounts of detectable ER, GR, and PR: the last receptor was almost always absent. A positive correlation between ER presence and tumor grade of differentiation was found in endometrial tumors from hormone-untreated patients. With the value of 142 fmol/mg DNA as the cut off point between high and low binding capacity, the frequency of the single receptors within the hormone-untreated cancer group ranged from 61% to 88%; ER and PR were simultaneously present in 55% of cases (they are tightly correlated in the different biopsies with respect to frequency and amount); ER-AR-PR were present in 45% and all the four receptors in 40% of cases. Slightly higher values were found in normal endometrium collected from hormone-untreated patients.

The comparative interaction of equimolar amounts of 1,2-dichloroethane and 1,2-dibromoethane with rat and mouse nucleic acids was studied in both in vivo (liver, lung, kidney and stomach) and in vitro (liver microsomal and/or cytosolic fractions) systems. In vivo, liver and kidney DNA showed the highest labeling, whereas the binding to lung DNA was barely detectable. Dibromoethane was more highly reactive than dichloroethane in both species. With dichloroethane, mouse DNA labeling was higher than rat DNA labeling whatever the organ considered: the opposite was seen for the bioactivation of dibromoethane. RNA and protein labelings were higher than DNA labeling, with no particular pattern in terms of organ or species involvement. In vitro, in addition to a low chemical reactivity towards nucleic acids shown by haloethanes per se, both compounds were bioactivated by either liver microsomes and cytosolic fractions to reactive forms capable of binding to DNA and polynucleotides. UV irradiation did not photoactivate dibromoethane and dichloroethane. The in vitro interaction with DNA mediated by enzymatic fractions was PB-inducible (one order of magnitude, using rat microsomes). In vitro bioactivation of haloethanes was mainly performed by microsomes in the case of dichloroethane and by cytosolic fractions in the case of dibromoethane. When microsomes plus cytosol were used, rat enzymes were more efficient than mouse enzymes in inducing a dibromoethane-DNA interaction: the opposite situation occurred for dichloroethane-DNA interaction, and this is in agreement with the in vivo pattern. In the presence of both metabolic pathways, addition or synergism occurred. Dibromoethane was always more reactive than dichloroethane. An indication of the presence of a microsomal GSH transferase was achieved for the activation of dibromoethane. No preferential binding in vitro to a specific polynucleotide was found. Polynucleotide labeling was higher than (or equal to) DNA binding. The labeling of microsomal RNA and proteins and of cytosolic proteins was many times lower than that of DNA or polynucleotides. The in vivo and in vitro data reported above give an unequivocal indication of the relative reactivity of the haloethanes examined with liver macromolecules from the two species and agree, on the whole, with the relative genotoxicity (DNA repair induction ability, mutagenicity and carcinogenicity) of the chemicals.

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