The analysis of urinary excretory products following the administration of known compounds is one of the classical methods for the study of their metabolism. The developments in paper chromatographic (1) and micro-analytic (2) technics and the use of glucuronidase hydrolysis (3) have considerably decreased the difficulties of investigating steroid metabolism by this method. Using these newer technics, we have studied the urinary excretion pattern of the major alpha-ketolic steroids after the administration of the six "active" adrenal cortical steroids to individuals with severe adrenal cortical insufficiency. We have found, as has been demonstrated for other steroids (4), that the major alpha-ketolic metabolites result from the reduction in ring A of the steroid nucleus to the 3-alpha-hydroxy pregnane derivatives (the socalled "tetrahydro" form) and that the hydroxyl and ketone groups on carbon atom 11 are interconvertible for corticosterone and 1 1-dehydrocorticosterone as well as for hydrocortisone and cortisone. METHODS I. TerminologySince steroid terminology is varied and the proper chemical names consume considerable space, the terms and abbreviations more commonly used in physiological research will be employed in this paper. Definitions and abbreviations are listed below.Alpha-ketolic steroids: Pregnane derivatives having 20-keto and 21-hydroxy substituents (i.e., alpha-ketol group). A4-pregnene-21-ol-3, 11, 20-trione.DOC; li-desoxycorticosterone; A'-pregnene-21-ol-3, 20-dione. These are listed in order of decreasing polarity. The acetate is indicated by the abbreviation ac.Alpha-ketolic steroid metabolites (AKSM): Steroids with the alpha-ketolic side chain found in the urine. These are detectable by reaction of the alpha-ketol side chain with alkaline blue tetrazolium to produce a blue color. The unmodified abbreviation H4 indicates reduction in ring A to form the 3a normal (i.e., pregnane) reduction product. In addition to the alpha-ketolic cortical hormones, the major metabolites are: H4F; tetrahydro-hydrocortisone; pregnane-3a, 11P, 17a, 21-tetrol-20-one. H4E; tetrahydro-cortisone; pregnane-3a, 17a, 21-triol-11, 20-dione. H4S; tetrahydro-11-desoxy-17-hydroxycorticosterone; pregnane-3a, 17a, 21-triol-20-one. H,B; tetrahydro-corticosterone; pregnane-3a, Ilfi, 21-triol-20-one. H4A; tetrahydro-dehydrocorticosterone; pregnane-3a, 21-diol-11, 20-dione. H4DOC; tetrahydro-l1-desoxycorticosterone; pregnane-3ca, 21-diol-20-one. Polarity: In the chromatograms, the most polar steroids (i.e., those with the most hydroxyl and keto substituents) appear in the slowest moving fraction, X, and the least polar in the fastest moving fraction, Z. (See III, B Paper chromatographic and micro-analytic technics.) 285

We investigated the dominant/recessive nature of the XR-1 mutant locus in intraspecies Chinese hamster ovary (CHO) hybrids and interspecies hybrids with human cell lines that possess different radioresistances. The XR-1 cell is abnormally sensitive to killing by gamma rays in the G1 phase of the cell cycle, while late-S-phase cells have wild-type resistance. [3H]Thymidine selection was used to eliminate the resistant S-phase population. In both intraspecies and interspecies hybrids, the XR-1 mutation is recessive to the wild-type cell and is not influenced by differences in chromosome ploidy. Analysis of hybrids between human ataxia telangiectasia fibroblasts AT5BI and XR-1 cells revealed that they possess different genetic defects as they complemented each other in three of four hybrids tested. These data suggest that the XR-1 locus is evolutionarily conserved between hamster and human cells.

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<* Method I. 1 Method II. Equal molar amounts of reactants were used. 6 Method II. One molar excess of aliphatic diamine used. d Synthesized according to Method II. Two molar excess of aliphatic diamine used. * Hydrochloride. 1 Picrate derivative. » Yield based on the amount of aliphatic diamine used. * This material solidified on standing to a white, low melting solid. * The abbreviation p. a. is used for picric acid, CiH2N30r.

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