DRUG METABOLISM IN LIVER TUMORS: PURIFICATION AND CHARACTERIZATION OF NADPH-CYTOCHROME-P450 REDUCTASE AND THE RESOLUTION OF MULTIPLE FORMS OF CYTOCHROME P-450

The hydroxylation of N- and O-methyl drugs and a polycyclic hydrocarbon has been demonstrated in microsomes prepared from two transplantable Morris hepatomas (i.e., 7288C. t.c. and 5123 t.c.(H). The hydroxylation rates of the drug benzphetamine and the polycyclic hydrocarbon benzo {(alpha)} pyrene by tumor microsomes were inducible 2 to 3-fold and 2-fold, respectively by pretreatment of rats with phenobarbital/hydrocortisone. Hepatoma 5123t.c.(h) microsomal hydroxylation activities were more inducible after these pretreatments than hepatoma 7288C.t.c. Two chemotherapeutic drugs (cyclophosphamide and isophosphamide) were shown to be mutagenic after activation by the tumor hemogenate with the TA100 strain of Salmonella typhimurium bacteria. NADPH-cytochrome P-450 was purified from phenobarbital/hydrocortisone treated rat hepatoma 5123t.c.(H) microsomes 353-fold with a specific activity 63.6 nmol of cytochrome c reduced per min per mg of protein. The purified enzyme, has an apparent molecular weight of 79,500 daltons, and contained an equal molar ratio of FMN and FAD, with a total flavin content of 16.4 nmol per mg of protein. The purified enzyme also catalyzed electron transfer to artificial electron acceptors with the K(,m) values of the hepatoma reductase similar to those of purified liver reductase. The K(,m) value of the hepatoma reductase (13 uM) for NADPH was similar to that of purified liver reductase (5.0 uM). In addition the purified hepatoma reductase was immunochemically similar to the liver reductase.^ Hepatoma cytochrome P-450, the hemeprotein component of the hepatoma microsomes of rats pretreated with phenobarbital/hydrocortisone. The resolution of the six forms was achieved by the DE-53 ion-exchange chromatography, and further purified by hydroxyapatite. The six different fractions that contained P-450 activity, had specific contents from 0.47 to 1.75 nmol of cytochrome P-450 per mg of protein, and indicated a 2 to 9-fold purification as compared to the original microsomes. In addition, difference spectra, molecular weights and immunological results suggest there are at least six different forms of cytochrome P-450 in hepatoma 5123 t.c.(H). ^

Natural remanent magnetization (NRM) from ODP Site 1263 covering magnetochron C20r and C21n and high-resolution bulk carbon isotope (d13C) records from Sites 702 and 1263

To explore cause and consequences of past climate change, very accurate age models such as those provided by the astronomical timescale (ATS) are needed. Beyond 40 million years the accuracy of the ATS critically depends on the correctness of orbital models and radioisotopic dating techniques. Discrepancies in the age dating of sedimentary successions and the lack of suitable records spanning the middle Eocene have prevented development of a continuous astronomically calibrated geological timescale for the entire Cenozoic Era. We now solve this problem by constructing an independent astrochronological stratigraphy based on Earth's stable 405 kyr eccentricity cycle between 41 and 48 million years ago (Ma) with new data from deep-sea sedimentary sequences in the South Atlantic Ocean. This new link completes the Paleogene astronomical timescale and confirms the intercalibration of radioisotopic and astronomical dating methods back through the Paleocene-Eocene Thermal Maximum (PETM, 55.930 Ma) and the Cretaceous-Paleogene boundary (66.022 Ma). Coupling of the Paleogene 405 kyr cyclostratigraphic frameworks across the middle Eocene further paves the way for extending the ATS into the Mesozoic.

Evaluation of statistical methods used in obtaining broadcast ratings. Report pursuant to section 136 of the legislative reorganization act of 1946, Public law 601, 79th Cong., and House resolution 108, 87th Cong.

Includes bibliography.

Independent regulatory commissions. Report of the Special Subcommittee on Legislative Oversight of the Committee on Interstate and Foreign Commerce (pursuant to section 136 of the legislative reorganization act of 1946, Public Law 601, 79th congress, and house resolution 56, as amended, 86th congress)

January 3, 1961.

Activity of the Committee on Intersate and Foreign Commerce, 84th Congress. Report of the Committee on Interstate and Foreign Commerce, pursuant to section 136 of the Legislative reorganization act of 1946, Public law 601, 79th Congress, and House resolution 105, 84th Congress .

Mode of access: Internet.

Interim report of the Subcommittee on Legislative Oversight, pursuant to section 136 of the Legislative reorganization act of 1946, Public law 601, 79th Congress, and House resolution 99, as amended, 85th Congress [on] Federal Communications Commission.

Mode of access: Internet.

Network broadcasting : report pursuant to section 136 of the Legislative Reorganization Act of 1946, Public Law 601, 79th Congress, and House resolution 99, 85th Congress

Mode of access: Internet.

Radio astronomy report; propagation through a disturbed ionosphere: effect upon range and angular resolution, Project Wide Band.

"RADC contract no. AF 30(602)-2077."

Asset disposition by the RTC including the present status of the SAMDA program : hearing before the Subcommittee on Financial Institutions Supervision, Regulation and Insurance, Resolution Trust Corporation Task Force of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, One Hundred Second Congress, first session, May 20, 1991.

Mode of access: Internet.

A study of mutual funds : prepared for the Securities and Exchange Commission. Report of the Committee on Interstate and Foreign Commerce, pursuant to section 136 of the Legislative reorganization act of 1946, Public law 601, 79th Congress, and House Resolution 108, 87th Congress.

Mode of access: Internet.