Retinoid protection against x-ray-induced chromatid damage in human peripheral blood lymphocytes.
Oral administration of isotretinoin (13-cis retinoic acid) was shown previously (Kraemer, K. H., J. J. DiGiovanna, A. N. Moshell, R. E. Tarone, and G. L. Peck. 1988. N. Engl. J. Med. 318:1633-1637) to reduce the frequency of skin cancers in xeroderma pigmentosum (XP) patients. The mechanism of protection was unclear. In the present study, x-ray-induced chromatid damage in PHA-stimulated blood lymphocytes from five XP patients receiving isotretinoin was approximately half that in blood samples from the same patients before or subsequent to treatment. The x-ray-induced chromatid damage in blood lymphocytes from a normal control was reduced significantly by cocultivation with blood or plasma from an XP patient receiving isotretinoin or by addition of 10(-6) M isotretinoin to cultures 1 h before x-irradiation. A similar reduction in x-ray-induced chromatid damage was reported previously by adding to the culture medium, mannitol, a scavenger of the free hydroxyl radical, or catalase, which decomposes hydrogen peroxide; both of these products are generated during ionizing radiation. The present observations suggest that isotretinoin acts as a scavenger of such radiation products, thereby providing protection against x-ray-induced chromatid damage.
Sanford
K K
KK
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Parshad
R
R
Price
F M
FM
Tarone
R E
RE
Kraemer
K H
KH
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002842:Chromatids / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000517:prevention & control; D014965:X-Rays; D014983:Xeroderma Pigmentosum / Q000150:complications
D015474:Isotretinoin