RAl)l()-PROTECTI\K ACIIOX OF 5-HYDROXYTRYPTAMINE 



sui\i\in^^ control rats, and an incidence of to If) i)cr cent diarrlioea amongst 

 protected animals, over the jjeriod during which most control animals die 

 {i.e. two to ten days after irradiation). 



Prolonged survival — Most protected rats surviving beyond 'M) da>'s, have 

 survived in good health for prolonged periods of up to twelve months, 

 although their body weight is reduced, greying of hair occurs with typical 

 distribution, and in odd animals sfjuamous cell carcinomata of skin have 

 appeared. 



fertility — Whilst reduced fertility has resulted, inter-breeding of protected 

 irradiated male and female survivors after 1000 r total body irradiation, 

 has resulted in a fair proportion of litters with offspring reduced in number 

 but apparently normal. Most offspring are successfully suckled and gain 

 weight at a normal rate. Bacq and Alexander^ state that female rats protected 

 by cysteamine, are permanently sterilized by 700 r X-rays. 



Protective dose of 5-0//T— Doses of less than O-SxlQ-^ moles afford 

 considerably less protection against acute lethality, but doses as low as 

 0-5 X 10 •* moles, reduce incidence of diarrhoea to 50 per cent, of the control 



value. 



Protection of locally irradiated skin — Rats receiving the protective agent 

 (5-OHT) parenteraily in doses of 0-5 x 10-^ moles before local irradiation of 

 skin with soft X-rays (30kV, H.V.D. 2 mm in tissue, dose of 4000 r at surface 

 of skin, field size 2-5 cm round circle), show greatly diminished reactions and 

 skin damage. Plate 1 shows the results of such an experiment. This protective 

 action for 5-OHT, is considerably greater, than the local protection afforded 

 by cysteamine in doses of 20 x 10-^ moles, despite the greater protective 

 action of the latter against acute lethality in rats from whole-body irradiation. 



Protective action of related indoles and histamine 



1-tryptophan — The parent amino acid, which gives 87 per cent protection 

 of polymer in vitro in concentrations of 8 x 10"* moles ^ fails to protect in vivo 

 in mice (1 x 10"^ moles) or in rats (200 mg/kg given 10 to 30 minutes pre- 

 ceding irradiation). Bacq and Alexander attribute the failure of aromatic 

 and heterocyclic amino acids to protect in vivo, as due to relative inability 

 to penetrate membrane barriers, by virtue of their carboxyl groups. 



Attempts to modify uptake of the amino acid 1-tryptophan, and 3,4- 

 dihydroxyphenyl alanine by pretreatment of rats with reserpine to release 

 catechol amines and 5-OHT, and an amine oxidase inhibitor (iproniazid) 

 to prevent destruction of any aromatic amines formed in tissues, ha\e failed 

 to yield significant protection attril^utable to amino acid incorporation in 

 the cells; 3,4-dihydroxyphenyl alanine itself in doses of 200 mg/kg in rats 

 causes pilierection and sympathetico-mimetic activity, but fails to afford 

 substantial radio-protection, as distinct from results recorded by Alexander 

 et al.^ for mice. 



Trvptamine 3-{beta-aminoethyi) indole — This unhydroxylated substance, is 

 the naturally occurring indole amine in invertebrate tissues^- and in equi- 

 molecular doses in mice gives substantial protection ^ From our own results, 

 it is a much weaker protective agent than 5-OHT in rats although its pharma- 

 cological behaviour is similar but also less intense. Contrary to the claim of 

 Bacq and Alexander- that tryptamine is not a vasoconstrictor, Reid^^ and 



172 



