Synthesis of liver cytochrome P-450b in a cell-free protein synthesizing system.
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Biomedical subjects
Publications and source records attributed to E Bresnick.
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We have tested the sensitivity of a cloned rat hepatocyte line, RL-PR-C, to aflatoxin B1 and benzo(a)pyrene as a function of population-doubling level. The cells were much more sensitive to the cytotoxic action of these agents subsequent to 230 population doublings. This sensitivity corresponded to the enhanced inducibility of aryl hydrocarbon hydroxylase activity by 3-methylcholanthrene.
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Sixty-two couples with infertility received infertility counseling along with the infertility investigation and treatment. At the end of the study a questionnaire was sent to all patients in order to evaluate the incidence of psychologic symptoms associated with their infertility and their response to counseling. The study confirmed the presence of a high incidence of emotional symptomatology in the self-selected patients. It showed that male partners are also affected, but less so. Finally, it has demonstrated that infertility counseling serves to enhance the quality of life in many patients who have become the victims of their "infertility crises."
The topical application of the promoter, 12-O-tetradecanoyl-13-acetate, on the shaved backs of mice was attended by a striking increase in the PGE concentration within epidermis as early as 1 h later. This increase peaked at 24 h but the prostaglandin value remained elevated for at least 48 h. PGF, on the other hand, showed only a modest increase in epidermis with a maximum at 12 h. By 48 h, the PGF concentration returned to normal.
In this report the ability of nuclei to carry out mixed function oxidase activity has been discussed. The properties of the nuclear system have been contrasted with those of microsomes and the localization of the nuclear mixed function oxidase has been definitively established. In addition, the nuclei have been shown to contain an inducible O-deethylase and epoxide hydrase(s). Finally, nuclei have been demonstrated to catalyze the formation of benzo[a]pyrene syn- and anti-diolepoxides, ultimate carcinogenic forms of this polycyclic hydrocarbon.
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A/J, C3H/HeJ, DBA/2J, and C57BL/6J mice have different susceptibilities to polycyclic aromatic hydrocarbon-induced pulmonary neoplasia, whereas the livers from these animals are uniformly resistant to the carcinogenic actions of these substances. After i.v. injection of [3H]-3-methylcholanthrene, radiolabel was detected in the DNA of both lung and liver of all these strains. The DNA was digested to deoxyribonucleosides and chromatographed on Sephadex LH-20. The amounts of nucleoside-bound adducts detected varied markedly with the different tissues and strains. These adducts were undetectable in liver DNA by 28 days. Although all lung preparations showed some reduction in adducts by 28 days, the amounts in A/J lung were always highest; this correlated with its high susceptibility to neoplastic transformation. In all preparations, radioactivity eluted from Sephadex LH-20 with the column void volume or with underivatized nucleosides. Tissue, but not strain differences were observed in these chromatographic profiles. The predominance of these early-eluting peaks in liver, rather than lung, suggests that they may represent noncarcinogenic lesions. This radiolabeled material remains uncharacterized, but some possibilities are discussed.
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The in vivo binding of [3H]benzo(a)pyrene (BP) and 3-[3H]methylcholanthrene (3MC) to liver and lung DNA was studied in A/J mice. Only in liver was there any reduction in total DNA-bound radioactivity between 4 h and 24 h after administration of the hydrocarbon. DNA was fractionated on Sephadex LH-20 after enzymatic digestion. A single deoxyribonucleoside-BP adduct was detected whereas two major 3MC-adducts were observed. Wtih both BP and 3MC, three additional peaks of radioactivity eluted rapidly in the lung DNA experiments while a fourth was noted with liver DNA. The nucleoside-bound adducts from lung represented a much larger proportion of the total radioactivity than with liver. In vitro analysis of 3MC binding to DNA showed the nucleoside-bound adducts to be predominantly deoxyguanosine-dependent but that the early peaks were independent of base suggesting binding to another part of the DNA molecule, perhaps phosphate, i.e, phosphotriesters.
The alkaline elution technique has been adapted for use in the assessment of DNA damage induced in the livers and lungs of mice after administration of an alkylating agent, methylemthanesulfonat (MMS). At 4 h after administration of MMS, damage ot DNA was readily demonstrable; the damage was repaired in liver by 24 h. The lung, particularly of the A/J mouse, exhibited an increased alkaline elution rate when compared to C57BL/6J, and repair was not entirely complete (as judged from the rate of alkaline elution of DNA) by 24 h. The rate of elution was dependent upon temperature. It is believed that this adaptation should have great utility in examining DNA repair in vivo.