Inhibition of heterochromatin condensation of human Y chromosome by distamycin-A.

Distamycin-A, an oligopeptide antibiotic with a N-methylpyrrole ring system and propionamide side chain, preferentially forms stable bonds with AT rich double stranded DNA. When introduced to cell cultures, it inhibits condensation of the heterochromatic region of the Y chromosome. The frequency of metaphases showing inhibition of heterochromatin condensation of the Y chromosome was found to be dependent on the treatment time and concentration of distamycin-A in the culture medium. When distamycin-A was added to a concentration of 100 micrograms/ml at the start of the culture (72 hours), the frequency of Y heterochromatin decondensation was found to be 48%, 30% and 6% in amniotic fluid, lymphocyte and fibroblast cultures respectively. The highest frequency of metaphases with decondensed Y heterochromatin were observed when distamycin-A treatment was carried out for the last 24 hours prior to harvest, the frequencies being 94%, 72% and 59% in amniotic fluid, lymphocyte and fibroblast cultures respectively. Increase in the concentration of distamycin-A from 25 micrograms/ml to 50 micrograms/ml during the last 24 hours of culture increased the incidence of metaphases with Y heterochromatin decondensation from 51% to 69% in amniotic fluid, 40 to 49% in lymphocyte and 29% to 31% in fibroblast cultures. Highest frequency of metaphases with Y heterochromatin decondensation were observed when the cultures were exposed to distamycin-A at a concentration of 100 micrograms/ml for the last 24 hours of culture.

Precocious desynapsis of XY-bivalent in mouse germinal cells: influence of mitomycin C on tumour-bearing and normal mice.

A comparative study on the cytotoxic potential of anticancer-antibiotic mitomycin C has been made on tumour-bearing and normal mice considering precocious desynapsis of sex bivalent as parameter. The study indicates a strikingly differential effect of the drug on the phenomenon in two different types of mice. The administration of mitomycin C at therapeutic dose although enhances the frequency of precocious desynapsis of XY-bivalent in non-tumour (normal) mice to a significant extent (compared to control), the same drug at the same dose fails to produce a similar effect on tumour-bearing specimens. Discussions have been made on: (i) the probable cause for this differential effect, (ii) the mechanism of mitomycin action on precocious desynapsis of sex bivalent and, (iii) the possible significance of the findings in relation to cancer chemotherapy.