Elevated serum cathepsin B1 and vaginal pathology after prenatal DES exposure.
Activities of the lysosomal enzymes, cathepsin B1 (CBI), beta-glucuronidase, and beta-N-acetyl-D-glucosaminidase, as well as sialyl transferase, alkaline phosphatase, and placenta-like alkaline phosphatase, were determined on blind-coded serums from 99 women exposed to diethylstilbestrol (DES) in utero and 40 unexposed subjects of comparable age range. Cathepsin B1 averaged 100%, 1040% (P less than 0.001), 2720 % (P less than 0.001), and 4760% (P less than 0.001) of controls in DES-exposed women with no genital tract abnormalities (N = 11), adenosis (N = 68), adenosis with concomitant dysplasia (N = 15), and clear-cell adenocarcinoma (N = 5), respectively. The later two groups also exhibited 0.01). Activities of the other four enzymes in serums of DES-exposed women were unchanged from those controls, suggesting that alterations in CBI were not due to generalized increases in lysosomal membrane instability or other gross cellular damage. In 2 DES-exposed women with clear-cell adenocardinoma, from whom serial samples were available, preoperative levels of serum CBl fell from a mean of 4280% to values indistinguishable from controls by 7--12 days after tumor excision, concurrently with objective signs of remission. Recrudescence of serum CBI levels preceded by at least 3 months clinical evidence of persistent adenosis accompanied by vaginal dysplasia. Although the nature of the increments in CBI-like activity in the majority of subjects with DES-related pathology remains to be determined, the findings may complement present methods of physical diagnosis and prognosis.
D000118:Acetylglucosaminidase / Q000097:blood; D000230:Adenocarcinoma / Q000139:chemically induced / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D002403:Cathepsins / Q000097:blood*; D004054:Diethylstilbestrol / Q000009:adverse effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D011247:Pregnancy; D012799:Sialyltransferases / Q000097:blood; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced / Q000601:surgery; D014625:Vaginal Neoplasms / Q000139:chemically induced* / Q000601:surgery
D004054:Diethylstilbestrol; D012799:Sialyltransferases; D000469:Alkaline Phosphatase; D005966:Glucuronidase; D000118:Acetylglucosaminidase; D002403:Cathepsins