• A comparative binding of platinum anti-tumour compounds to plasma proteins in the rat (in vivo) and mouse (in vitro).

      Perera, A; Jackson, H; Sharma, H L; McAuliffe, C A; Fox, Brian W; Department of Chemistry, University of Manchester Institute of Science and Technology, UK. (1992-12)
      Plasma protein binding of 195mPt-labelled cisplatin, carboplatin and iproplatin has been studied in vivo in rat and in vitro in mouse, using both electrophoresis and trichloroacetic acid precipitation. After intravenous injection plasma clearance rates were biphasic for all 3 compounds, (t1/2 alpha, 13-17 min) but cisplatin was retained thereafter longer than the others. By 5 min, gel electrophoresis showed protein labelling with all 3 drugs but none involved low mol.wt. proteins (< 16 kDa). At 2 h a notable proportion of the protein bound platinum was associated with the latter components. There was a general resemblance between the distribution patterns of cisplatin and carboplatin whereas iproplatin showed a persistent retention of the label with time to higher mol. wt. proteins. From in vitro incubation with mouse plasma, rates of interaction respectively were cisplatin t1/2 alpha, 35 min, beta 8 h, carboplatin t1/2, 44 h and iproplatin t1/2, 104 h. By electrophoresis the protein bound fraction pattern (1 h) was again similar for cisplatin and carboplatin with virtually no binding to low mol. wt. proteins. After 24 h these were now involved to a high degree (40%). Iproplatin showed relatively marked binding to proteins of higher mol. wt. but no transfer with time to the low mol. wt. protein zone. A possible explanation is the need for in vivo metabolism for this compound as manifest in the rat. It is suggested that the significance of interaction with low mol. wt. proteins merits further investigation in relation to the antitumour and toxicological actions of these drugs.
    • A comparative study of the distribution in the male rat of platinum-labelled cis-dichlorodiammine platinum (II), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum (I), and cis-dichloro-bis-cyclopropylamine platinum (II).

      Harrison, R; McAuliffe, C A; Zaki, A; Baer, J; Sharma, H; Smith, A; Jackson, H; Fox, Brian W; Inorganic Chemistry, UMIST, Oxford Rd Manchester, M13 9PL (1983)
    • Screening for mutagenic hazards of potential chemical contraceptives in male.

      Bateman, A J; Jackson, H; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (1974)
    • Spermatogenic and mutagenic damage after paternal exposure to systemic indium-114m.

      Hoyes, Katherine P; Sharma, Harbans L; Jackson, H; Hendry, Jolyon H; Morris, Ian D; Department of Experimental Radiation Oncology, Paterson Institute for Cancer Research, Manchester, United Kingdom. (1994-08)
      The cytotoxic and mutagenic consequences of systemic administration of 114mIn have been examined. Adult male rats were dosed intraperitoneally with 14.8 or 3.7 MBq/kg 114mIn. Approximately 0.25% of the injected radioactivity was localized within the testis by 24 h and was retained with an effective half-life of 49.5 days. Breeding studies were started 3 days after injection, males being housed with two females for seven consecutive mating trials of 19 days, separated by 2 days. Indium-114m caused a reduction in litter size and an increase in the incidence of pre- and postimplantation losses and dominant lethal mutations. These effects became evident from 24 days but were most marked between 87-126 days after treatment and persisted up to 147 days. When animals were mated 200 days after treatment, no significant changes were observed. In a parallel study, administration of 14.8 MBq/kg 114mIn resulted in decreased testis and epididymal weight and sperm reserves. Maximal reduction occurred between 87-108 days after injection followed by recovery toward control values, but neither organ had reached normal levels at 200 days. A single dose of 3.7 MBq/kg, however, had no effect on reproductive organ weight or sperm content. Male F1 progeny from the 14.8 MBq/kg group of the second mating period (commencing at 24 days) displayed decreased testis weights and sperm content and provoked a higher incidence of dominant lethal mutations. This effect was not observed in male progeny from any other time or the alternative dose level.