Sex-linked Recessive Lethals Research Articles

Evaluating the effect of low dose rate of gamma rays in germ cells of Drosophila melanogaster

Purpose: Evaluation of genetic risk in germ cells is still matter of research, mainly due to their role in the transmission of genetic information from one generation to another. Although numerous experiments have been carried out in Drosophila in order to study the effect of radiation on germ cells, the role of dose rate (DR) has not been fully explored. The purpose of this study was to evaluate the action of DR on the radioprotection induction on male germ cell of D. melanogaster.Material and method: The productivity and the sex-linked recessive lethal (SLRL) tests were used to evaluate the radio-sensitivity of different states of the germ line of males. Two-day-old males of Canton-S wild type strain were pretreated with 0.2 Gy at 5.4 or 34.3 Gy/h of gamma rays from a 60Co source, three hours later, they were irradiated with 20 Gy at 907.7 Gy/h. Thereafter, each single male was crossed with 3 five-day old Basc virgin females, that were replaced every other day by new females. This procedure was conducted three times, to test the whole germ cell stages.Results: Females crossed with males irradiated with 0.2 Gy at both DR tested, laid a higher number of eggs than control, but egg-viability was reduced. On the other hand, in the group of 0.2 Gy + 20 Gy -combined treatments- the total number of eggs laid decreased only when 0.2 Gy were delivered at 34.3 Gy/h however, the egg-viability increased. The dose of 0.2 Gy at both DR did not modify the baseline frequency of SLRL. A tendency to decrease in the frequency of lethals in brood III was found in combined treatments at both DR.Conclusion: The fact that 0.2 Gy at 5.4 or 34.3 Gy/h induced an increase in the egg-viability and a tendency to decrease the genetic damage in pre-meiotic cells provoked by 20 Gy, might indicate the induction of any mechanism that could be interpreted as radioprotection in male germ cells of D. melanogaster. Results emphasize the need to carry out more studies on the effect of the DR on the induction of genetic damage in germ cells.

Effects of historic radiation dose on the frequency of sex-linked recessive lethals in Drosophila populations following the Chernobyl nuclear accident

Contrary to the effects of high doses of radiation, the effects of low doses of radiation are still being investigated. Low doses and their non-targeted effects in particular are of special interest for researchers. The accident that occurred at the Chernobyl Nuclear Power Plant (NPP) gives researchers the opportunity to view these effects outside of a laboratory environment. For this paper, the relationship between low historic radiation doses and the persistent genetic damage observed in populations of fruit flies (Drosophila melanogaster) around the Chernobyl NPP over 3 years will be investigated. Data from Zainullin et al. (1992) on the frequency of sex-linked recessive lethals (SLRLs) in D. melanogaster around the Chernobyl NPP. To calculate the absorbed historic external dose, a method based on the Gaussian plume model was used to find the external dose from both plume shine and ground shine. The dose attributed to the ground shine dose made a greater contribution to the overall absorbed external historic radiation dose than the plume shine dose. For earlier generations of Drosophila living in the radioactive contaminated sites, the SLRL frequencies appeared to correlate with the dose in a linear no-threshold relationship. The later descendent generations appeared to have developed a radio-adaptive-like response. This work contributes to the understanding of historic dose effects on wildlife health following the accidental release of high mount of radioactive materials into the environment.

Coffee mitigates cyclophosphamide-induced genotoxic damage in Drosophila melanogaster germ cells

In the present study, coffee (CF) was evaluated for its protective effects against genotoxic damage and oxidative stress induced by the chemotherapeutic drug, cyclophosphamide (CPH). The sex-linked recessive lethal (SLRL) test was employed to study the induction of mutations in the larvae as well as in all the successive germ cell stages of treated males. Control and treated third instar larvae were used to monitor the biomarkers of oxidative stress response such as glutathione content (GSH), glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content). Our results demonstrated that co-administration of CF (2%) with CPH (3 mM) has significantly reduced CPH-induced lethal mutations in the germ cells of larvae and adult flies. The reductions observed in mutation frequencies were: 75% in larvae and 62.4% in the adult. Significant enhancement in antioxidant enzymatic levels: CAT (46.6%) > SOD (43.0%) > GST (42.4%) > GSH (31.6%) and reduction in MDA levels (32.05%) in the pretreated third instar larvae demonstrated the antioxidant activity of CF against CPH-induced oxidative stress. The findings from the present study suggest that the Drosophila model is an ideal one for evaluating the antigenotoxic and antioxidant activity of complex mixtures like CF.

Protective effects of tea polyphenols and \u03b2-carotene against \u03b3-radiation induced mutation and oxidative stress in Drosophila melanogaster

BackgroundThe commonly consumed antioxidants β-carotene and tea polyphenols were used to assess their protective effects against γ-radiation induced sex-linked recessive lethal (SLRL) mutation and oxidative stress in Drosophila melanogaster. Third instar larvae and adult males of wild-type Oregon-K (ORK) were fed on test agents for 24 and 72 h respectively before exposure to 10Gy γ-irradiation. The treated/control flies were used to assess the induction of SLRLs. We also evaluated antioxidant properties of these phytochemicals in the third instar larvae.ResultsDifferent stages of spermatogenesis in adult males showed a decrease in γ-radiation induced SLRL frequencies upon co-treatment with test agents. A similar trend was observed in larvae. Furthermore, a significant increase in antioxidant enzymatic activities with a decrease in malondialdehyde content was observed.Conclusionβ-carotene and tea polyphenols have exerted antigenotoxic and antioxidant effects in Drosophila. This study demonstrated the suitability of Drosophila as an alternative to mammalian testing for evaluating the antigenotoxic and antioxidant activity of natural products.

Ameliorative effects of gallic acid, quercetin and limonene on urethane-induced genotoxicity and oxidative stress in Drosophila melanogaster

The main objective of our present work was to ascertain the efficacy of Drosophila melanogaster model for assessing antigenotoxic and antioxidant effects of dietary phytochemicals gallic acid (GA), quercetin (QC) and limonene (Lim) against urethane (URE), a genotoxic environmental carcinogen. Oregon-K (ORK) adult male flies were fed GA, QC and Lim in combination with URE (20 mM) in 10% sucrose for 72 h. Third instar larvae were fed instant medium containing the above phytochemicals and URE for 24 h. Sex-linked recessive lethal (SLRL) test and assays for estimating glutathione content (GSH), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content) were performed. Adult feeding experiments demonstrated that co-treatment of flies with URE and the test phytochemicals has significantly decreased the frequencies of SLRL mutations in all the germ cell stages when compared to that with URE alone. Larval feeding experiments also showed a similar pattern. The above results correlate well with antioxidative potentials of the test agents where we observed the elevated enzymatic levels with a significant reduction in MDA level in Drosophila larvae. The results further suggest that the dietary phytochemicals have an antioxidant and antimutagenic property which can be assessed using D. melanogaster.

Combining molecular docking and 3-D pharmacophore generation to enclose the in vivo antigenotoxic activity of naturally occurring aromatic compounds: Myricetin, quercetin, rutin, and rosmarinic acid

Considering the controversial results concerning the antimutagenicity of some phenolic compounds recorded in the literature, the antigenotoxic effects of four selected phenolic compounds, myricetin, quercetin, rutin, and rosmarinic acid, against DNA damage induced by alkylation with ethyl methanesulfonate (EMS), were evaluated in Drosophila melanogaster males using the sex-linked recessive lethal (SLRL) test. To assess the protective effects against DNA damage, D. melanogaster males were exposed to a monofunctional alkylating agent EMS in concentration of 0.75ppm, 24h prior to one of the selected phenolic compounds in the concentration of 100ppm. The possible differences in mechanisms of protection by selected compounds were determined by molecular docking, after which structure-based 3-D pharmacophore models were generated. EMS induced considerable DNA damage as shown by significant increase in the frequency of germinative mutations. The frequency decreased with high significance (p<0.001***) after post-treatments with all selected phenolic compounds. Further, docking analysis revealed EMS pre-bond conformations against guanine and thymine as a necessary condition for alkylation, after which resulting O6-ethylguanine and O4-ethylthimine were docked into the active site of O6-alkylguanine-DNA alkyltransferase to confirm that particular lesions are going to be repaired. Finally, myricetin and quercetin protected dealkylated nucleotides from further EMS alkylation by forming the strong hydrogen bonds with O6-guanine and O4-thymine via B ring hydroxyl group (bond lengths lower than 2.5Å). On the other side, rutin and rosmarinic acid encircled nucleotides and by fulfilling the EMS binding space they made an impermeable barrier for the EMS molecule and prevented further alkylation.

Protective role of methanol extracts of Gentiana asclepiadea L. and G. cruciata L. against genotoxic damage induced by ethyl methanesulfonate

The methanol extracts from the underground and aerial part of the two species of Gentiana genus, Gentiana asclepiadea L. and Gentiana cruciata L. from Serbia, were investigated for their antigenotoxic activity against wellestablished mutagenic agent ethyl methanesulfonate (EMS) using the in vivo sexlinked recessive lethal (SLRL) test on Drosophila melanogaster. For this purpose, three days old Canton S males were treated with the potent mutagen EMS in concentration of 0.75 ppm, alone and combined with methanol extracts obtained from underground or aerial part of G. asclepiadea and G. cruciata in concentration of 5%, separately. Although EMS in concentration of 0.75 ppm increased the mutation frequency in all three broods, post-treatments with methanol extracts obtained from the underground and aerial part of G. asclepiadea and G. cruciata in concentration of 5%, respectively, drastically reduced the frequency of sex-linked recessive lethal mutations induced by EMS. Compared to the sucrose, as a negative control, methanol extract obtained from underground part of G. cruciata showed the most potent antigenotoxic activity. Extracts from the underground and aerial part of the two species of Gentiana genus, G. asclepiadea L. and G. cruciata L. from Serbia used in our experiments showed a clear antimutagenic effect, reducing the frequency of mutations induced by a strong mutagen such as EMS.

Genotoxic damage induced by isopropanol in germinal and somatic cells of Drosophila melanogaster

Isopropanol (isopropyl alcohol, 2-propanol, IPA) is a volatile solvent widely used in domestic or industrial environments and reported as innocuous in various test systems. The aim of this work was to search for in vivo genotoxic effects of IPA in Drosophila melanogaster, studying its ability to induce nondisjunction (ND) in females, sex linked recessive lethals (SLRL) in males, and somatic mutation and/or recombination (SMART) in larvae. Treatments were acute (60min) and were administered via inhalation. IPA had low toxicity in adult flies (75% IPA mortality index, MI=12.7% (females) and 2.6% (males)) and larvae (MI=14.3%, 75% IPA). Female fertility was severely affected during the first 24h (brood I, BI) after treatment, but, afterwards, control values were recovered. IPA induced a 50-fold increase of ND (%) in 24h old females, and a six-fold rise in 4–5 d old BI offspring. Nondisjunction frequencies (%) in the offspring of broods II to V (24h in each case) were similar to control values. IPA doses of 25% and 50% (v/v), tested in 24h old females, showed a significant dose-dependent increase of ND(%)in BI only, with control values in subsequent broods. Flies gave normal offspring when kept in regular media for 24h before mating. The eye spot test (SMART) showed a significant increase at 50% IPA (p<0.05, m=2), but the response was not dose-dependent. IPA failed to induce SLRL in any of the spermatogenesis stages tested. These findings suggest that the main effect of IPA is to induce chromosomal malsegregation; IPA must be present at the resumption of M-phase I after fertilization, to exert these effects. The alcohol does not affect DNA directly, but perturbations of the nuclear membrane may be responsible for induction of ND.

CYTOGENETIC STUDIES OF X-RAY AND INGESTED P32 INDUCED SEX-LINKED RECESSIVE LETHALS IN DROSOPHILA MELANOGASTER

Male flies were either irradiated with 1000 r or fed a sugar solution containing Pa/sup 32/. The latter flies attained an average activity of 75 C. The males were immediately mated with unirradiated females according to the brood pattern technique. Chromosomal aberrations (deletions, translocations, and inversions) were recovered following treatment with either mutagen. The distribution of point mutation lethals induced on the X chromosome by P/sup 32/ was identical to the one found after x-ray treatment. The highest frequency of sex-linked recessive lethals in the P/sup 32/ series was found on days 7 and 8, as compared with day 5 for the x-ray series. The sterile period in the x-ray series following the exhaustive mating system used may be attributed partially to dominant lethals, lack of functional sperm, and to meiotic or mitotic inhibition due to irradiation. P/sup 32/ incorporated into the DNA of mature sperm was recovered 7 to 8 days after a single meal, under conditions of excessive mating, which coincides with maximum genetic effect. Thus the results favor the concept that the period of maximum DNA synthesis corresponds to the period of maximum lethal induction and/or of chromosome breakage. (H.H.D.)

RADIOSENSITIVITY IN DIFFERENT STAGES OF SPERMATOGENESIS IN DROSOPHILA MELANOGASTER

The male flies of various ages were irradiated with 1150- to 3300-r doses of Co/sup 60/ gamma radiation to elucidate the relative radiosensitivity in different stages of spermatogenesis. This was evaluated by studying the sensitivity pattern for different kinds of mutations, such as visibles, sex- linked lethals, II-III translocations, and induced crossovers in males. A peak in the frequency of recessive sex-linked lethals was observed on day 5 after irradiation, while translocation frequency showed a peak on day 7. The frequency of visibles showed no peak, but the statistical calculation suggested an increase in frequency up to day 5. A period of excessive sterility was observed on days 7 and 8 or days 8 and 9 after irradiation. The first crossovers were observed on day 6 or 7, concurrently with a low fertility but prior to the minimum of fertility. The time required for spermiogenesis should be about 6 to 7 days at 25 deg C in adult males. It was found that the radiosensitivity of fully mature sperms (day 1) was somewhat higher than that of nearly mature sperms (day 2). With further immaturity an increasing sensitivity was obseived for all effects studied up to day 5 or 6.more » However, if sterility is used as a measure of radiation effect, the maximum occurs on days 8 and 9. (TCO)« less

Mutagenic Effect of Three Nitrogenous Fertilizers on Drosophila melanogaster

The present study was carried out in order to evaluate the mutagenic effect of 3 nitrogenous fertilizers; urea, ammonium nitrate and calcium nitrate; on Drosophila melanogaster. Newly hatched larvae were treated with the LC25 and LC50 of the 3 tested nitrogenous fertilizers. The classic sex-linked recessive lethal (SLRL) test was used to detect the differential mutagenic effect of the fertilizers on the 3 germ stages. The results showed that all fertilizers exhibited variable mutation frequencies in the different broods of spermatogenesis after a single treatment. Urea exhibited a direct mutagenic effect on post-meiotic stages whereas ammonium nitrate and calcium nitrate revealed an indirect mutagenic effect on meiotic and pre-meiotic stages. The electrophoretic separation of proteins (SDS-PAGE) showed that treatment with these fertilizers resulted in polymorphetic changes in different low and high molecular weight protein bands, causing alteration in the electrophoretic patterns and densities of proteins. This study showed that the tested nitrogenous fertilizers possess mutagenic potentialities which are related to their nitrogen content.

The Genetic Effect of the Combined Action of Vincristine and Fennel Plant Extract on the Germ Cells of Drosophilla melanogaster

This study was designed to investigate the mutagenic potentiality of the anticancer drug vincristine and fennel plant extract on Drosophilla melanogaster using two test systems, the sex linked recessive lethal (SLRL) and estimating the activity of cholinesterase enzyme (ChE) in F1 and F2 bar eye females and F2 wild types males. A wild type Strain Oregon-R (or-R) male flies of D. melanogaster were treated on a medium containing a concentration of one of individually of the two agents, followed by combined treatment in an alternative way of fennel extract followed by vincristin, then vincristin followed by fennel extract and finally the two agents together. The results showed no significant increase in the percentage of the S.L.R.L in all stages of spermatogenesis in all treatments. Meanwhile, vincristine and fennel plant extract showed a genotoxic effects in the three categories of the two generations of S.L.R.L, F1 females heterozygous F2 bar eye females and F2 wild type males on the genetic background of ChE in all treatments.

Genotoxicity of paracetamol on the germ cells of Drosophilla melanogaster

Paracetamol is a common analgesic and antipyretic drug. The aim of the present study is to determine the potential genetic effects of Paracetamol in Drosophilla melanogaster using two methods: Sex Linked Recessive Lethals (SLRL) test and effect of Paracetamol on enzyme activity using spectrophotometric analysis. Three concentrations of drug were used (5, 10, and 20 mM). The results reveal significant differences in S.L.R.L, except spermatozoa stages showed insignificant increases when the data of the four broods were considered all together in three treatments. Meanwhile, Paracetamol showed a genotoxic effects in the three categories of the two generations of S.L.R.L, F1 heterozygous females, F2 bar eye females and F2 wild type males on the genetic back ground of Cholinesterase in all treatments.

Study of Genotoxic Effect of Lorazepam(ativan) on Drosophila melanogaster

The mutagenic potentialities of psychoactive drug, lorazepam was tested in Drosophila melanogaster using two test systems, the sex-linked recessive lethals test (SLRL) and the estimation of the activities of the enzymes cholinesterase (CHE) and aliesterase (AliE). Org K, male flies of Drosophila melanogaster were reared on a medium containing two concentrations of the drug, 5 and 10 mg/100 ml medium, and screened for sex-linked recessive lethals. The results indicated that significant number of recessive lethals were induced in Drosophila in all stages of spermatogenesis except in spermatozoa stage at the two doses of the drug, indicating that lorazepam(ativan) is capable of inducing sex-linked recessive lethal mutations in Drosophila melanogaster. Meanwhile, the drug showed a mutagenic effect on the genetic background of each of CHE and AliE, which proves the mutagenic potentiality of the drug.

Untersuchungen über mutagenität und toxizität von Captan bei Drosophila

Abstract Captan, a fungicide, was tested for mutagenicity and toxicity in adult males of Drosophila melanogaster. A potent mutagen, the alkylating agent Trenimon, was used as a positive control. Captan was applied to the flies in two different ways and in various solvents. Toxicity was estimated from the ratios of induced mortality and sterility of the treated males. Mutagenicity was determined from the frequencies of sex-linked recessive lethals in pre- and post-meiotic germ cell stages scored with the Basc method. Trenimon was found to be highly mutagenic at a non-toxic concentration. Captan, however, was not mutagenic either at low, non-toxic or at high, toxic concentrations. Even in combination with the solvent dimethyl sulfoxide Captan showed no mutagenicity. Captan is also not mutagenic in maize and mice as shown by various authors. In contrast to this, mutagenic activity of Captan has been demonstrated in the host-mediated assay, Neurospora, yeast, different tissue cultures and bacteria. To explain the discrepancy between our results and those found in other organisms we assume that, in Drosophila, Captan is inactivated before it reaches the germ cells.

Sex ratio among offspring of childhood cancer survivors treated with radiotherapy.

It has been postulated that paternal gonadal exposure would increase the sex ratio by inducing X-chromosomal dominant lethals but that maternal gonadal exposure would decrease the sex ratio by inducing recessive sex-linked lethals. We therefore evaluated the sex ratio (male-to-female ratio) of children born to survivors of childhood cancers in Denmark. Children with cancer were identified from the Danish Cancer Registry from 1943 to 1996 and their offspring from the Central Population Registry. Radiation treatments were determined from records within the Cancer Registry and gonadal radiation exposures were estimated based on the cancer being treated and the likely proximity of the radiation fields to the gonads. Overall, 1100 survivors of childhood cancer became the parents of 2130 children. The sex ratio for male (0.99) and female (1.00) cancer survivors was similar and did not differ significantly from the Danish population (1.06). Radiotherapy did not influence the sex ratio of the children of either male or female survivors, and there was no evidence for dose-related changes over categories of estimated dose to parental gonads. We saw no consistent association between the sex ratio and the interval between cancer diagnosis of the parent and birth of the child. This nationwide study provides no support for the hypothesis that radiation exposure to the gonads results in an inherited genetic effect that would be manifested by a change in the sex ratio of children born after exposure. It may be, however, that sex ratio alterations are not a good or even a valid indicator of possible genetic effects in humans.

Adaptive response to alkylating agents in the Drosophila sex-linked recessive lethal assay

The adaptive response to alkylating agents was studied in Drosophila assays under various treatment procedures. Pre-treatment of males as well as treatment of females with low doses of EMS (0.05–0.1 mM) did not affect sex-linked recessive lethal (SLRL) rates induced by high doses of this mutagen (10 mM, various feeding duration) in mature sperm cells. Pre-treatment of males with a low dose of MMS (0.1 mM) enhanced mutagenesis induced by the high dose of EMS (10 mM) at different stages of spermatogenesis, the observed effects exceeding the additive action of both mutagens. On the contrary, larval pre-treatment with the adaptive dose of EMS (0.05 mM) resulted in resistance of their germ cells to higher doses of EMS (1 mM). Specifically, offspring production increased while dominant lethality in F 1 as well SLRL frequency in F 2 was significantly reduced as compared with the effects of larval exposure to the challenge dose. Under the conditions tested, the adaptive response of germ cells to alkylating agents was demonstrated in larvae, but not in adult flies.

Effect of mutagen-induced cell lethality on the dose response of germline mutations.

Molecular tests for mutations require a sample of tissue from which DNA is extracted, to determine the presence or absence of one or more mutations per sample. To ensure mutation fixation each sample must consist of an equal number of cells that have had one or more DNA replications. In an in vivo test, surviving stem cells compensate to give the same number of cells per sample, leaving as the only evidence for stem cell lethality the increase in mutants of clonal origin because the mutant clone developed from a population of fewer stem cells. A problem is that an increase in mutagen dose increases stem cell death, resulting in a decreased number of surviving target cells, thus giving a downward bias of samples with one or more mutations per sample. To compare in vivo tests with molecular tests we will use as a model system the sex-linked recessive lethal (SLRL) test for germ cell mutations in Drosophila melanogaster. Spermatogonia cells in male larvae were exposed to ENU and mutations detected in sperm cells from adults. The same SLRL data were analyzed by two methods: (1) The conventional analysis of SLRL data, in which each mutation of a cluster of mutations of common origin was counted. (2) An analysis was used to simulate a sample for molecular analysis by determining mutations per male with an equal size sample of progeny per male. With this second analysis a correction factor is required based on the change in cluster size of mutants of common origin.

Mutagenicity of sodium azide and its metabolite azidoalanine in Drosophila melanogaster

The mutagenic and toxic activities of sodium azide (NaN3 ) and its organic metabolite l-azidoalanine [N3–CH2–CH(NH)2–COOH] were examined in the different stages of spermatogenesis in Drosophila melanogaster. Both azide and azidoalanine were toxic to the injected males, but azidoalanine was significantly less toxic than sodium azide. Following the injection with 0.2μl of these compounds in the hemocoel of young adult wild-type males, the minimum concentrations of these compounds with complete toxic effects (zero survival) were 40mM sodium azide and 160mM azidoalanine. Sex-linked recessive lethals were scored by the Muller-5 method in three successive broods, representing sperms (brood A), spermatids (brood B), and a compiled group of meiotic and premeiotic germ cell stages (brood C). The results provide strong experimental evidence that azidoalanine is significantly (p<0.01) mutagenic to all stages of spermatogenesis in Drosophila melanogaster. Sodium azide, however, was not significantly (p>0.05) mutagenic and did not increase the rate of sex-linked recessive lethals over those produced by the control group injected with 0.45% NaCl. These results indicate the requirement of metabolic activation of azide in Drosophila as a prerequisite for its mutagenic effects.

Evaluation of the database on mutant frequencies and DNA sequence alterations of vermilion mutations induced in germ cells of Drosophila shows the importance of a neutral mutation detection system

The vermilion gene in Drosophila has extensively been used for the molecular analysis of mutations induced by chemicals in germ cells in vivo. The gene is located on the X-chromosome and is a useful target for the study of mutagenesis since all types of mutations are generated. We have critically evaluated this system with respect to sensitivity for mutation induction and selectivity for different types of mutations, using a database of more than 600 vermilion mutants induced in postmeiotic male germ cells by 18 mutagens. From most of these mutants the mutation has been analysed. These data showed 336 base substitutions, 96 intra-locus DNA rearrangements and 78 multi-locus deletions (MLD). Mutants containing a MLD were either heterozygous sterile or homozygous and hemizygous lethal. The distribution of both basepair (bp) changes and intra-locus rearrangements over the coding region of the vermilion gene was uniform with no preferences concerning 5′ or 3′ regions, certain exons, splice sites, specific amino acid changes or nonsense mutations. Possible hotspots for base substitutions seem to be related to the type of DNA damage rather than to the vermilion system. Gene mutations other than bp changes were examined on sequence characteristics flanking the deletion breakpoints. Induction frequencies of vermilion mosaic mutants were, in general, higher than those of vermilion complete mutants, suggesting that persistent lesions are the main contributors to the molecular spectra. Comparison of induction frequencies of vermilion mutants and sex-linked recessive lethal (SLRL) mutants for the 18 mutagens showed that the sensitivity of the vermilion gene against a mutagenic insult is representative for genes located on the X-chromosome. The effect of nucleotide excision repair (NER) on the formation of SLRL mutants correlated with an increase of transversions in the vermilion spectra under NER deficient conditions. Furthermore, the clastogenic potency of the mutagens, i.e., the efficiency to induce chromosomal-losses vs. SLRL forward mutations, shows a positive correlation with the percentage of DNA deletions in the molecular spectra of vermilion mutants.