Theophylline induced differentiation provides direct evidence for the deregulation of c-myc in Burkitt's lymphoma and suggests participation of immunoglobulin enhancer sequences.

Most of the evidence that supports the hypothesis that the c-myc gene is abnormally regulated in Burkitt's lymphoma (BL) is indirect. The putative abnormal expression of c-myc is likely, at least in part, to be a consequence of the usurpation of its regulatory sequences by immunoglobulin enhancer elements, which are invariably juxtaposed to c-myc by the translocations associated with this tumor (C. M. Croce, J. Erikson, A. Ar-Rushdi, D. Aden, and K. Nishikura, Proc. Natl. Acad. Sci. USA, 81: 3170-3174, 1984). We have developed a differentiation induction model system to examine this issue more directly. In a variety of non-BL cell lines, differentiation induction results in the down-regulation of c-myc (G. P. Studzinski, A. K. Bhandal, and Z. S. Brelvi, Proc. Soc. Exp. Biol. Med., 179: 288-295, 1985; Y. Matsui, R. Takahasi, K. Minara, T. Nakagawa, T. Koizumi, Y. Nakao, T. Sugiyama, and T. Fugita, Cancer Res., 49: 1366-1371, 1985; T. Mitchell, E. Sariban, and D. Kufe, Mol. Pharmacol., 30: 398-402, 1986; Z. S. Brelvi, and G. P. Studzinski, J. Cell. Physiol., 128: 171-179, 1986). Since BL is of B-cell origin, differentiation is associated with persistent or increased expression of immunoglobulin genes. Therefore, if c-myc and c-mu are coregulated in BL via immunoglobulin enhancer sequences, persistent or increased expression of the c-myc gene, rather than down-regulation, should occur in differentiated BL cells. Differentiation was induced in four BL cell lines with theophylline (7 x 10(-3) M), and mRNA was examined by Northern blot analysis. In all four BL lines studied (JD38, AG876, KK124, and Daudi), there was persistent or increased expression of both c-mu and c-myc genes (detected with a third exon c-myc probe), in contrast to the decreased expression of the c-myc gene observed in the three Epstein-Barr virus transformed lines studied (A3317, TC84, and CB34). In the BL cell line, JD38, the c-myc gene is truncated (the second and third exons are translocated to chromosome 14 while the first exon remains on chromosome 8). In this line, we demonstrated that theophylline induced differentiation results in down-regulation of the first exon while the level of expression of the translocated second and third exons remains unchanged or increases.(ABSTRACT TRUNCATED AT 400 WORDS)

Concentration of serum testosterone in XY sex reversed horses.

The XY Sex Reversal Syndrome of the horse is a condition associated with female or intersexual development in genetic males. In our previous study, 38 sex reversed XY mares were classified according to behavior, gross clinical phenotype, gonadal status, and H-Y phenotype. Four classes were described, ranging from potentially fertile female (Class I) to virilized intersex (Class IV). In the present study, serum testosterone concentrations were measured in 29 sex-reversed XY mares, 3 normal mares and 3 normal stallions. Serums were obtained during the breeding season (March-August), and were stored at -70 C until assayed. Serum testosterone concentrations in the normal XX mares ranged from nondetectable to 0.41 ng/ml; in normal XY stallions, from 1.04 ng/ml to 2.4 ng/ml; and in XY mares, from nondetectable to 5.4 ng/ml. Sex reversed mares previously assigned to Class I or II had serum testosterone concentrations ranging from nondetectable to 0.22 ng/ml. Serum testosterone concentrations in XY mares were correlated with sex phenotype and behavior. Although the range of steroid concentrations among XY mares may be quantified more accurately with increased sampling, serum testosterone concentrations can be used currently as an added parameter for study of the sex reversed condition.