388 . ORNL UNCLASSIFIED . We Do NO WALIOWY * . .. i . LET nare CZY***TAK PIST TW . . ORNE-p-388 DTIE-P CONF-744-1 OCT $1964 RECENT DEVELOPMENTS IN RESEARCH ON RADIATION AND CHEMICAL MUTAGEN EFFECTS IN INSECTS* 3. C. von Dorstel Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee - - ---LEGAL NOTICE This report na prepared as an acenant of Governor ont sponsored work. Hether the United hom, ww Who Canot, we w poruna kostimewa ball C o un: A. Nakon my warranty or m ountathma, express or implied, wou netract the neer mey, potom, o wonders of the wormation contained in who report o that when we of nay ludormation, apparatue, method, or proceso disclosed in the report may not infringe poimainly und Motos of 1. Aww.w my lewe lether with moment when we , or for more power thung from the w ames were martw.. w , or conductor in we mport. Ao low where, porno action model of the Comment" machentono way we phopen or www of the Commutateur et plerae of mocha contracur, W hel neeh employee or contractor of the Commission, or employee of such contractor properes, Werminata, « worden mec w mary motorola porta a Memphyod or cruce with the Commuteria, o no employment with me contractor. *Research sponsored by the U. S. Atomic Energy Commission under contract with the Union Carbide Corporation. " Y ...NL O . .. ? ... Running head: Radiation and Chemical tagen Effects Send proofto: Dr. R. Er von Borstel Biology Division Oak Ridge National Laboratory P. O. Box Y .. Ridge, Tennessee 37831 . *3. 9 , 7 * * ** * . .- ' . . im VW , , St Y er!! .F 2 i : - vr. * 2 The induced sterility discussed at this conference can be divided .. into two major components, dominant lethality and true sterility from gonial cell killing. There are of course other types of sterility such as sperm inactivation. Also there is an effect of the radiation whereby the males are weakened, which is a kind of pseudosterility. This weakening of the difficulty since males released in the field must be vigorous to successfully compete. I shall discuss some of the possible ways to lessen the male- weakening effect. after presenting a short surmary of recent advances made in the theory of dominant lethality. I would like to present a model, though not a unique one, which provides a reasonable explanation for most of the parameters associated with dominant - : - ' . . Interni. . 3 - lethality induced in sperm. The theory is important for the irradiation-of-male method of insect control because it has inherent in its consequences an istivities. explanation of the resistance to radiation of the sperm of Lepidoptera. There is considerable circumstantial evidence that induced dominant lethality is associated with chromosome breakage. One of the best pieces of evidence for this is that a diploid sperm is exactly twice as sensitive to radiation as a haploid sperm (Mortimer and von Borstel, 1963), and this effect 1s equivalent to the cüpacity of radiation to induce chromosome breaks in a ploidy serie: (Conger and Johnston, 1956). These are the only two radiation effects in ploidy series which are the same, since higher ploidies usually 11.- confer a kind of protection against radiation in growing plants or in insect si C- TA embryos. . 3 .. - S ' 1 Let is assume that dominant lethality in the wasp Habrobracon or in the fly Drosophila is induced, by formation of chromosome bridges; this is an assumption based on a considerable body of data (cf. von Borstel, 1960). The initial exponential component of a dose-hatchability curve following irradiation of sperm could come from terminal deletions of the chromosome arms which form chromosome bridges when a new chromosome is synthesized, and this would follow the expression (1) S = e-KD where S is the surviving fraction, D is the dose of radiation, and k is the sensitivity of the chromosome. The multihit component of the dose-hatchability curve (and Lepidoptera have only the multihit type of sperm curve) could possibly come from formation of dicentric translocations at a limited number of binomially distributed sites in a sperm where the chromosomes lie close enough together for a translocation to be formed when both are broken. This would follow the expression S = (1 - (1 - e-KD, 2, (2) where m is the number of sites; the 2 in the exponent refers to the two chromosomes that must be broken within the site. Together, equations (3.) and (2) are S = e-*2D(1 - (1 - e-k2D, 2, m (3) which can give an explicit, though, as mentioned before, not necessarily a unique, description of the dose-hatchability curve following irradiation of the sperm of Hebrobracon or Drosophila The model deriving from equation (2) has been developed earlier (von Borstel; 1960; Bender and Wolit, 1961; Wolff, 1961) to describe RASA - - - - - . kat - ' HTI - - *..** 27 A . VT . PAK dose-action data on the induction of dicentric translocations, and it was used to analyze data on detachments, through translocations, of attached-X chromosomes (Wolff, 1962; Parker, 1963). Since the frequency of total induced reciprocal translocations can be measured independently, and since these should be equal in number to the lethal dicentric translocations formed and measurable by equation (3), it is expected that a test of consistency of the above model will be made soon. There are at least three possible ways in which the radiation effect on the weakening of male insects might be lowered: (1) lowering the dose to that just above where 100% killing of the gonial cells can be accomplished, (2) fractionating the doses, and (3) irradiating the males with radiation of higher LET. It is not necessary for the irradiation-of-male method to succeed that 99.9%, 99%, nor 90% of the sperm contain induced dominant lethals. It would work even at lower lethal limits providing that the females (which usually have to be released as well) have no viable eggs and that neither males nor females will have repopulation of the gonial cells. This may be possible in certain insects and should certainly be investigated when other methods fail. Also, although hatchability is a convenient and accurate criterion of damage, reduced adult survival is all that really matters; with flies and wasps the dose can probably be reduced about 20% over that used to obtain 99% dominant lethality, providing again that the gonial cell populations are eliminated. This reduction of doses for the same final effect on viability for adults and eggs may vary from insect to insect and ... . . should also be investigated. . Dose-fractionation allows time for certain types of radiation damage on VEEL RSS ... to recover between the doses. Interestingly enough, the dose-fractionation . ' . ..- M A MY ' ,' T T -*, KVET " 24MTITI - - - ... - - . .. - - -- - -- : . . allows recovery of most types of damage excet the genetic and dominant lethal damage induced in sperm (cf. Sobels, 1963). It might be possible to increase the vigor of males without reducing their lethal capacity by using fractionated or chronic radiation. Dominant lethality is approximately doubled by 1 MeV neutron over that oü equivalent doses (kilorep) of gamma or X radiation, whereas recessive lethality only increases by about 50% (Edington and Randolph,' 1958). This should be investigated for the effect on weakening of males. It is possible that a nuclear reactor or some type of heavy ion generator may be the radiation source of choice for certain insects. Also, weakening of the males is lessened if the insects can be irradiated as adults rather than as pupae, or as late pupae rather than as early pupae. The great potential for the use of chemosterilants for insect control has barely begun to be explored since it was first suggested by Knipling (1959). The chemicals are in many ways simpler to use than the radiation and the possibility exists that it can be used in the field. Of course the hazards are great too; long-lived chemosterilants could possibly be as hazardous as heavy fallout from nuclear detonations, and trace amounts might be carried by the very insects that are being treated in the field. Nevertheless, different chemosterilants have different actions. Certain of them undoubtedly induce differing ratios of dominant lethal to recessive lethal mutations. For example, the alkylating agent ethyl methanesulfonate appears to induce a low ratio of dominant lethal to recessive lethal mitations, and the ratio is increased when nitrogen mustard is used (Löbbecke and von Eorstel, 1962). Apholate appears to have a higher dominant lethal to -P . I. recessive lethal ratio than either APO or MAPO in Neurospora (Kaney and Atwood, 1964). Such relations should be sought among the better chemosterilants and then these should be tested for long-term somatic effects in mice such as ability to induce tumors or to reduce the age of senescence. The somatic studies program directed by A. C. Upton at the Biology Division, Oak Ridge National Laboratory, could perhaps be called upon or used as a model for studying these types of effects. It is possible that an excellent chemosterilant could be found for use in the field which would have no debilitating effects on hunians or on vertebrates in general. . . .. REFERENCES .. . -. -- - - - -er. man Bender, M. A and S. Wolff 1961 X-ray-induced chromosome aberrations and reproductive death in mammalian cells. Am. Nat. 95: 39-52. Conger, A. D. and A. H. Johnston 1956 Polyploidy and radiosensitivity. Nature, London 178: 271. Edington, C. W. and M. L. Randolph 1958 A comparison of the relative effectiveness of radiations of different average linear energy transfer on the induction of dominant and recessiire lethals in Drosophila. -- -- - Arsin man and was carries winess Intele nter Genetics 43: 715-727. Kaney, A. R. and K. C. Atwood 1964 Radiomimetic action of polyimine chemosterilants in Neurospora. Nature 201: 1006-1008. Knipling, E. F. 1959 Sierile-male method of population control. Science 130: 902-904. Lóbbecke, E.-A. and R. C. von Borstel 1962 Mutational response of Habrobracon oocytes in metaphase and prophase to ethyl methanesulfonate and nitrogen mustard. Genetics 47: 853-864. Mortimer, R. K. and R. C. von Borstel 1963 Radiation-induced dominant lethality in haploid and diploid sperm of the wasp Mormoniella. Genetics 48: 1545-1549. Parker, D. R. 1963 On the nature of sensitivity changes in oocytes of Drosophila melanogaster. In Repair from Genetic Radiation Damage and Differential Radiosensitivity in Germ Cells. Pergamon Press, London. pp. 11-19. von Borstel, R. C. 1960 Sulla natura della letalita dominate indotta dalle i W - man o . radiazioni. Atti Assoc. Genet. Ital. 5: 35-50. - r . 1 . L' !! 7 WA 3. Wolff, S. 1961 Sone postirradiation phenomena that affect the induction of chromosome aberrations. J. Cell. Comp. Phys. 58 (Suppl. 1): 151-162. Wolff, s. 1962 The kinetics for two-break chromsome exchanges. J., Theoret. Biol. 3: 304–314. 7 .' . - :- DATE FILMED 1/ 30 /64 44. - LEGAL NOTICE This roport was propared as an account of Government sponsored work. Neithor the United Suator, nor the Commission, nor any person noting on behall of the Commission: A, Makos may warranty or representation, expressed or implied, with respect to the scou- racy, completeness, or wofulness of the Information contained in the report, or that the wave of any laformation, appuratus, method, or procou discloned in this report may not latringe privately owned rigata; or B. Aspumos aay Habilities with roopoot to the une of, or for damages rosulting from the un of any information, apparatus, method, or prooow disolound in this roport. As weed in the above, "person aottag on behalf of the ComAlaston" Includes wy one ploys or contractor of the Commission, or employs of such contractor, to the extent that such employs or contractor of the Commission, or employee of woh contractor prepares, disseminatos, or provides socos, to, any information pursuant to bilo onployment or contract with the Commission, or his employment with such contractor. END