By immunoprecipitation analysis, enhanced p53 expression was detected in 3 of 4 adult T‐cell leukemia (ATL) cell lines, 1 of 3 HTLV‐I‐infected cell lines and 1 of 5 fresh ATL samples, compared with phytohemagglutinin‐stimulated peripheral blood lymphocytes. Among these 5 high expressers, p53 missense mutations were indicated in 2 ATL cell lines and 1 fresh ATL sample by extensive p53 cDNA and genomic DNA polymerase chain reaction single‐strand conformation polymorphism analysis. No mutation was found throughout the entire coding region of the remaining 2 high expressers (1 ATL and 1 HTLV‐I‐infected cell lines) and low expressers of p53 (2 HTLV‐I‐infected cell lines). Tax oncoprotein expression was found in these 2 high p53 expressers in which p53 mutation was not present, but not in low p53 expressers or cells carrying this mutation. The levels of p53 mRNA were similar among the samples regardless of p53 levels. Posttranscriptional mechanisms other than missense mutation would thus appear to increase p53 in the Tax‐expressing cells hut not in cells containing undetectablc levels of Tax. No complex formation between p53 and Tax was observed.

Although nanomaterials are being used in various fields, their safety is not yet sufficiently understood. We have been attempting to establish a nanomaterials safety-assessment system by using biomarkers to predict nanomaterial-induced adverse biological effects. Here, we focused on microRNAs (miRNAs) because of their tissue-specific expression and high degree of stability in the blood. We previously showed that high intravenous doses of silica nanoparticles of 70 nm diameter (nSP70) induced liver damage in mice. In this study, we compared the effectiveness of serum levels of liver-specific or -enriched miRNAs (miR-122, miR-192, and miR-194) with that of conventional hepatic biomarkers (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) as biomarkers for nSP70. After mice had been treated with nSP70, their serum miRNAs levels were measured by using quantitative RT-PCR. Serum levels of miR-122 in nSP70-treated mice were the highest among the three miRNAs. The sensitivity of miR-122 for liver damage was at least as good as those of ALT and AST. Like ALT and AST, miR-122 may be a useful biomarker of nSP70. We believe that these findings will help in the establishment of a nanomaterials safety-assessment system.

To determine the minimum volume of blood required to transmit human T- cell leukemia virus type I (HTLV-I), heparinized blood was collected from a virus-infected female rabbit and aliquots of 10, 5, 1, 0.5, 0.1, and 0.01 mL were transfused into groups of two male rabbits each. All 10 rabbits transfused with 10 to 0.1 mL and 1 of 2 rabbits transfused with 0.01 mL seroconverted for HTLV-I after 2 to 4 weeks. HTLV-I- producing lymphoid cell lines of recipient origin were established from one seroconverted rabbit of each aliquot group. To determine the ability of passive immunization to protect against HTLV-I infection, two groups of three rabbits were first transfused with 5 mL of blood from the same virus-infected rabbit and then infused after 24 or 48 hours with 10 mL of HTLV-I immune globulin (77 mg/mL of IgG) prepared from seropositive healthy persons. None of the 24-hour immunization group seroconverted for HTLV-I during the observation period of six months; however, all of the 48-hour immunization group became seropositive after 2 to 4 weeks. These results indicate that HTLV-I can be transmitted with as little as 0.01 mL of virus-infected blood, and that passive immunization is effective in preventing cell-to-cell infection of HTLV-I when given within 24 hours of transfusion of virus- infected blood.

Prophylactic effect of human T cell leukemia virus type I (HTLV-I) immune globulin (HTLVIG) against milkborne transmission of HTLV-I was investigated in a rabbit model. Four litters (A-D: 7, 5, 7, and 7 offspring, respectively) born to an HTLV-I-infected rabbit were used. Litters A and D were allowed to grow normally as controls, while litters B and C were given weekly intraperitoneal inoculation of HTLVIG four times until weaning at 4.5 weeks of age. Only 1 (8.3%) of the 12 HTLVIG-inoculated rabbits, compared with 6 (42.9%) of the 14 control rabbits, seroconverted for HTLV-I. Gene amplification detected the presence of HTLV-I proviral sequences in all of the seroconverted but in none of the seronegative rabbits. These results suggest that passive immunization is effective in preventing dam-to-offspring transmission of HTLV-I.

Four rabbits inoculated intravenously with milk cells from 4 post-partum women seropositive for human T-cell leukemia virus type I (HTLV-I) and one rabbit inoculated with semen cells from a seropositive healthy man seroconverted for HTLV-I after 3-5 weeks but no seroconversion occurred in 2 rabbits inoculated with milk cells from a seronegative mother or with heated (56 degrees C, 30 min) milk cells from a seropositive mother. Attempts were made to isolate HTLV-I from peripheral blood lymphocytes harvested 5-15 weeks after cell inoculation and cultured in the presence of interleukin-2. An HTLV-I-carrying lymphoid cell line of rabbit origin was established from a rabbit inoculated with milk cells. Another long-term culture, derived from a rabbit inoculated with semen cells, also expressed HTLV-I antigens and harbored virus particles. Furthermore, transfusion of 20 ml of blood from all 5 seroconverted rabbits, but not from the 2 seronegative ones, caused seroconversion in normal recipient rabbits after 4-6 weeks.