Takashi Mima

Establishment of human squamous carcinoma cell lines highly and minimally sensitive to bleomycin and analysis of factors involved in the sensitivity

Human squamous carcinoma cell lines that were highly and minimally sensitive to bleomycin were established from clinical specimens and designated as SCCKN and SCCTF, respectively. Although these cell lines showed a similar growth doubling time in vitro, SCCTF was approximately ten times less sensitive to bleomycin than SCCKN. The bleomycin high and low sensitivities were stable even at the 70‐cell passage level in vitro. In addition, nude mouse tumors produced by SCCTF were less sensitive to bleomycin than those produced by SCCKN, and the ratio of the mean tumor weight in bleomycin‐treated mice to that in control mice was 89.2% in SCCTF and 18.8% in SCCKN. As compared with SCCKN, SCCTF also was less sensitive to peplomycin (5‐fold), mitomycin C (2.3‐fold), cisdiammine dichloroplatinum (2.5‐fold), and vincristine (6.5‐fold). Analyses of low bleomycin sensitivity showed that SCCTF had an approximately 20% decreased cellular accumulation and retention of bleomycin, 1.2‐fold increase of bleomycin hydrolase activity, elevated DNA repair activity, and increased poly(adeno‐sine diphosphate‐ribose) polymerase activity as compared with SCCKN.

Serum dipeptidyl peptidase activities as a possible marker of oral cancer

Serum glycyl‐1‐prolyl 4‐methyl‐coumaryl‐7‐amide (gly‐pro‐MCA) hydrolase (DPP IV) and L‐lysyl‐L‐alanyl β‐naphthylamide (lys‐ala‐β NA) hydrolase (assumed to be DPP II) activities were measured in patients with oral squamous cell carcinoma and healthy subjects. The mean serum DPP IV activity of all cancer patients was significantly (P < 0.001) decreased, compared with that of healthy subjects. Although there was no significant difference between the stages by International Union Against Cancer (UICC) classification (1978), DPP IV levels tended to change dynamically, reflecting the clinical status during therapies. The serum DPP IV activity of patients with a fair prognosis was significantly elevated toward the normal range, whereas the activity of patients with a poor prognosis was significantly decreased (P < 0.05). In contrast, the mean serum lys‐ala‐β NA hydrolytic activity of cancer patients was significantly (P < 0.001) increased, compared with that of healthy subjects, and was changed reciprocally to DPP IV activity. The correlation of these two serum enzyme activities with tumor weights also was observed in animal models using nude mice transplanted with human KB carcinoma cells and hamsters transplanted with BHK21 cells. These results indicate that these serum enzyme levels may become an aid for the diagnosis of malignant tumors and for estimating the prognosis of the patients.