WE describe a group of poisons which produce constant and widespread effects in laboratory animals when administered by various routes. The toxicological action of the prototype of the group, 2 chlorovinyldichloroarsine (lewisite I), was recognised early in 1940 and most of the subsequent investigations were carried out with this compound. Information about some of the other members is less full, because only a small amount of material was at our disposal; but there is good reason to believe that in general all behave in much the same way, and similarity of action after skin application means that closely related effects follow other routes of administration. For convenience we shall refer to these poisons as the lewisite group, despite differences in chemical constitution of individual members. The group includes lewisite I (CHClCHAsCl,), lewisite I1 [(CHClCH),AsCl], phenyldichloroarsine, phenyldibromoarsine and phenyldifluoroarsine. All are fairly heavy liquids, with pungent and often characteristic odours. They are soluble in many organic solvents but tend to be changed in water. The LD,, for various routes are summarised in the table; some figures for hydrolysed lewisite I ( 2 chlorovinylarseniousoxide), usually referred to as lewisite oxide, are included. Undiluted compounds were used for skin and subcutaneous tests. Dilution, when necessary, was carried out with arachis oil or liquid paraffin : this was essential for intravenous injection.We also determined, for lewisite I, the smallest skin dose producing serious, though not fatal, changes. Adopting biliary lesions as the memure of casualty production in guinea-pigs, the smallest effective dose appears to be one-fifth to one-third the LD,,. I n rabbits, one third the LD,, is the smallest dose capable of inducing definite blood changes.Fatal doses.
Variations in the shape of the nucleus have been described in different animal cells. In addition, the following factors have been shown to be responsible for nuclear shape: (1) Surface tension : when this is equal over the surface of the nuclear membrane, the nucleus tends towards the spherical condition. When surface tension varies over the interface between nucleus and cytoplasm, nuclear polymorphism may result. (2) Mechanical deformation of the nucleus is common and may be due to various causes, chief amongst which are: (a) Pressure from cytoplasmic inclusions, e.g. fat, lecithin, and yolk; (b) Tonofibrillae; (c) in striated muscle, the influence of the Membranes of Krause which constrict the nucleus along its length--and limit its ends--by their prolongation from the myofibrillae into the sarcoplasm. (3) The centrosome, which has been shown (in the resting cell) often to repel that part of the nuclear membrane which is nearest to it. (4) The relation between cell shape and nuclear shape has been briefly discussed. It has been noted that the nucleus never comes into contact with the cell membrane, except in the rarest instances due to the intervention of mechanical factors. Evidence has been brought forward in favour of our view that there is a mutual repulsion between cell membrane and nuclear membrane. (5) Canaliculi and incisions in the nuclear membrane have been described in various cells. (6) The unfolding of such incisions during development and differentiation of some such cells has been described. (7) Intranuclear rodlets and their importance in the maintenance or the modifying of nuclear shape have been discussed. (8) Mitotic division and a certain degree of nuclear differentiation have been shown often to be incompatible--thereby accounting for amitosis in certain highly specialized nuclei. (9) The need for care in distinguishing between nuclear incisions and genuine amitotic division of nuclei has been emphasized.
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