Male F-344 rats were given [ 3 H]aflatoxin B, (AFBj) in the drinking water at three exposure levels (0.02, 0.6, 20 /*g/l, resulting in average dose levels of 2.2, 73, 2110 ng/kg per day). After 4, 6 and 8 weeks, DNA was isolated from the livers and analyzed for aflatoxin-DNA adducts. The level of DNA adducts did not increase significantly after 4 weeks, indicating that a steady-state for adduct formation and removal had nearly been reached. At 8 weeks, the adduct levels were 0.91, 32 and 850 nucleotide-aflatoxin adducts per 10 9 nucieotides, i.e. clearly proportional to the dose. At the high dose level, a near 50% tumor incidence would be expected in a 2-year bioassay with F-344 rats while the low dose used is within the range of estimated human dietary exposures to aflatoxin in Western countries. The proportionality seen between exposure and steady-state DNA adduct level is discussed with respect to a linear extrapolation of the tumor risk to low dose.

1395 Methoxy-Gruppe liegt ungefahr in der Ring-D-Ehene. Die Ehenen des Biphenylsystems sind um einen Winkel von 32,3" bzw. 34,4" gegeneinander verdreht. Ganz ahnliche Verhaltnisse liegen auch im Bulbocapnin-methojodid [7] [9] vor. Die uber die beiden unahhangigen Molekeln in der asymmetrischen Einheit der Zelle gemittelten Bindungslangen und Bindungswinkel finden sich in Figur 3. Rindungslungen (e.s.d. 0,Ol A) Bindungswinkel e.s.d. 0,7")

Summary. The synthesis of a new, boron-containing analogue of phenylalanine is described. Carboranylala.nine (Car) carries a 1,2-carborane cage in place of the benzene ring of phenylalanine. It is obtained by the reaction of derivatives of propargylglycine with decaborane. Possibilities of practical application derive from the facile neutron activation of boron nuclei with mass number 10.o-Carborane (1, 2-C~BloH12) and its C-derivatives [ 21 display icosahedral geometry. The dimensions of the cage are only slightly larger than the space occupied by a benzene ring rotating about its C(l)-C(4) axis, and the two carbon atoms participate in the delocalized bonding. It thus appears that o-carboranylalanine (1; Car) would be sufficiently similar to phenylalanitie in order to be an interesting analogue for probing the role of this amino acid in certain biologically active peptides. The likeness becomes apparent from the Figure.The possible role of 1 as a probe becomes even more intriguing if one considers the interaction of boron with thermal neutrons, having v N 2,220 m/s at 0.025 eV '31 : Natural boron is composed of 18.45% 1% and 81.5Sy0 IlB; the former has a large capture cross section for thermal neutrons of 3,900 barns (= 10--2* 1112). Very pure [loB]-decaborane, the starting material for [10B]-o-carboranylalariine, has been prepared in this laboratory (E. Escher). From the above data it would appear that o-carboranylalanine with -on the average -two or more 10R nuclei would be an excellent molecule for producing ionizing radiation in biological materials.Boron, introduced into certain parts of the animal or plant body, has been used for auto-radiographic purposes [3], and for the treatment of neoplastic diseases (cancer) [4]. o-Carboranylalanine, as a component of peptides such as peptide hormones, might offer an especially attractive means of transporting via the blood )This work was supported by the Schweizerischer Nationalfonds zur Forderung der wissenschaftlichen Fovschung, and is part of the doctoral thesis of 0. L. Abbreviations according to [l] and [Z]. For the new amino acid, o-carboranylalanine, the abbreviation Car is proposed.HELVETICA CHIMICA ACTA -Vol. 59, Fasc. 6 (1976) -Nr. 225 2185 CarFhe stream rather high concentrations of boron to specifically defined areas (target cells and target organs). Starting materials for the synthesis of 1 (Scheme) were the bis(acetonitri1e)-decaborane complex [5], and L-phthalyl-propargylglycine methyl ester [6] : (4Condensation (c) was carried out according to the general procedure of Heying [7], and immediately and stereospecifically gave pure, crystalline 2 in a moderate yield (50-60%). Concentrated boiling HC1 solution removed both protecting groups (reaction (d)) ; the free amino acid 1 was readily obtained, although in a small yield (22%). More diluted HC1-solution in acetic acid, according to the general procedure of Sheehan et al. [8], selectively hydrolysed the methoxycarbonyl group to give the N-phthalyl-L-amino-acid 3 (Ieaction (e)) . 86HELVETICA CHIMI...

Overall, biogas is a promising alternative for the future, because its resource base is widely available, and single farms or small local cooperatives might start biogas plant operation.