Reproduction Nutrition Development, formerly Annales de Biologie Animale Biochimie Biophysique

In jawed vertebrates theV‐(D)‐Jrearrangement is the main mechanism generating limitless variations of antigen‐specific receptors, immunoglobulins (IGs), andT‐cell receptors (TCRs) from few genes. Once the initial diversity is established in primary lymphoid organs, further diversification occurs inIGs by somatic hypermutation, a mechanism from which rearrangedTCRgenes were thought to be excluded. Here, we report the locus organization and expression of theT‐cell receptor gamma (TCRG) genes in theArabian camel (Camelus dromedarius). Expression data provide evidence that dromedary utilizes only twoTCRG V‐Jgenomic arrangements and, as expected,CDR3 contributes the major variability in theVdomain. The data also suggest that diversity might be generated by mutation in the productively rearrangedTCRGVgenes. As forIGgenes, the mutational target is biased towardGandCbases and (A/G/T)G(C/T)(A/T) motif (orDGYW). The replacement and synonymous substitutions (R/S) ratios inTCRGVregions are higher forCDRthan for framework region, thus suggesting selection toward amino acid changes inCDR. Using the counterpart humanTCRγδ receptor as a template, structural models computed adopting a comparative procedure show that nonconservative mutations contribute to diversity inCDR2 and at the γδVdomain interface.

Tryptizol^® [amitriptyline HCl (AT); El-Kahira Pharmacological and Chemical Co., Cairo, Egypt], a widely used antidepressant drug in Egypt, was evaluated for its genotoxicity. The evaluation was performed in somatic (bone marrow) and germ (spermatocytes) cells, as well as well as the sperm morphology (i.e., head and tail) and count of the resulting sperm. Three doses were tested (low, medium, and high); they were chosen according to the drug manufacturer. The low-dose group received orally 1 mg/kg body weight (b.w.) daily for a total period of 1 month; the medium-dose group received 1 mg/kg b.w. daily for 15 days and 2 mg/kg b.w. daily for another 15 days; and the high-dose group received 1 mg/kg b.w. daily for 10 days, then 2 mg/kg b.w. daily for another 10 days and, finally, 4 mg/kg b.w. daily for 10 more days. The results showed that AT treatment induced structural and numerical chromosome abnormalities in somatic cells (bone marrow) and germ cells (spermatocytes). Moreover, AT significantly reduced both the mitotic index and meiotic activity after the different treatments used. AT was found to increase significantly the incidence of sperm-cell head and tail abnormalities. The sperm-cell count was also significantly decreased with the 3 doses tested. In general, results of chromosome abnormalities in both somatic and germ cells as well as sperm morphology and count showed that the effect of AT was dose dependent. The results of the current study showed that AT is a genotoxic agent for both somatic and germ cells and should be taken under special precautions and medical supervision.