Percentage of <i>Allium</i> cells with various chromosomal aberrations after exposure for 48 hr to ZDV or NVP.

a<p><i>Sticky chromosomes</i> refer to the tendency of chromosome arms or entire chromosomes to stick together.</p>b<p><i>Chromatin bridges</i> occur in mitosis when the telomeres of sister chromatids fuse together and fail to completely segregate into their respective daughter cells. ^c<i>Vagrant forms</i> refer to chromosomal formations different from the normal formation during mitosis.</p>d<p><i>Binucleated cells</i> have more than one nucleus. ^e<i>Multipolar mitosis</i> occurs when the chromosomal material is pulled to more than two poles, resulting in the formation of a corresponding number of nuclei. ^f<i>Chromosomal fragments</i> refer to fragments of a chromosome that may be lacking a centromere and so is often lost when the cell divide.</p

Dominant lethal assay (DLA) after males were treated with Zidovudine or Nevirapine for eight weeks.

<p>DLA simulates when the “father-only” is ARV treated.</p><p>EMS = Ethylmethylsulfonate (one-time dose); ZDV = Zidovudine; NVP = Nevirapine.</p>a<p>Number of pregnancies observed after 1∶1 mating.</p>b<p>Number of pregnancies before/after adding dams with heavy arterial linings to the pregnancy count. Dams with heavy arterial lining of the uterus and/or uterine fluids indicate fertile mating had occurred but was aborted early.</p>c<p>Number of implants per pregnant dam or the average from all pregnant dams in the group.</p><p>Differences in number of aborted pregnancies at week 4 versus week 8 was not significant.</p><p>Dominant lethal assay (DLA) after males were treated with Zidovudine or Nevirapine for eight weeks.</p

<i>Allium cepa</i> root length grown for 96 hr in zidovudine (black line) or nevirapine (grey line).

<p>Expressed as percentage of the unexposed control with value 34.6±2.7 mm (mean ± SE; n = 5 bulbs/group). The drug concentration giving half maximal root growth length (EC₅₀) for zidovudine (ZDV) was 65.0 µM, and for nevirapine (NVP) was 92.5 µM. At the 400, 800 and 1200 µM doses, roots from the NVP-exposed groups were significantly longer than those from the ZDV-exposed groups.</p

Impact of ZDV and NVP on the mitotic index of <i>Allium cepa</i> root cells^a exposed for 48 hr.

a<p>Each experimental group contained 10 bulbs and 2–3 root tips from each bulb were squashed together on one slide. On each slide 40–100 cells were examined. Values shown are means ± standard deviation of the mean.</p>b<p>EC₅₀ is the concentration of drug that inhibits <i>Allium</i> root growth length by 50%; 10% of EC₅₀ is 5% of total root growth length.</p>c<p>For the percentage of cells in mitosis: for unexposed vs.32.5 µM ZDV, <i>p</i> = 0.02; for ZDV 50% of EC₅₀ vs. NVP 50% of EC₅₀, <i>p</i> = 0.03. All other associations were statistically non-significant.</p

Proportion of surviving pups and their sex ratios in relation to dose and parental treatment.

<p>Proportion of surviving pups was determined while weaning the pups at age 4 weeks.</p><p>ZDV = Zidovudine; NVP = Nevirapine.</p>a<p>Four males from each dose mated five females each to give a total of twenty dams per dose. Ten of these dams were untreated (“father-only” treated groups) while the other ten had received the same dose as the males (“both-parents” treated groups) for 56 days before mating. Harem mating was done by co-housing one male and five females for 10 days without checking for vaginal plugs.</p>b<p>We compared the survival proportion of the treatment groups to that of the untreated control group (70.8%) using the binomial test. The proportions of surviving pups were significantly different for most treatment groups except for that of the ZDV 100 mg/kg at both first and repeat mating; for NVP 50 mg/kg at first mating and for NVP 150 mg/kg at repeat mating.</p><p>Proportion of surviving pups and their sex ratios in relation to dose and parental treatment.</p

Gestation period in relation to dose and the parental mouse treatment.

<p>Four males per dose mated five females each to give a total of twenty dams per dose. Ten of these dams were untreated (“father-only” treated groups) while the other ten had received the same dose as the males (“both-parents” treated groups) for 56 days before mating. Harem mating was done by co-housing one male and five females for 10 days without checking for vaginal plugs. ZDV = Zidovudine; NVP = Nevirapine; EMS = Ethylmethylsulfonate (one-time dose); SD = Standard Deviation.</p>a<p>Average gestation period obtained for dams mated to males on therapy at the time of mating.</p>b<p>Average gestation period obtained for dams mated to males previously treated but have not received ARVs for another spermatogenic cycle (56 days) to check if effects could resolve. Thus only the females were still on therapy at the repeat mating.</p>c<p>Both parents had been on therapy but at repeat mating, only the dams were currently on therapy as the males had been withdrawn for one full spermatogenic cycle.</p>†<p>Single birth recorded, thus SD could not be calculated.</p><p>Using ANOVA, significantly shorter gestation periods was observed only for the NVP “both-parents” treated groups at first mating and for the ZVP “father-only” treated groups at repeat mating when the treatment groups were compared to the untreated control.</p><p>Gestation period in relation to dose and the parental mouse treatment.</p

Micrographs of chromosomal aberrations seen in the treatment groups.

<p>A – Normal metaphase from the negative control group. *B – Vagrant metaphase form with misaligned chromosomes in cell from 32.5 µM ZDV. *C – C-Metaphase chromosomes seen only in cells exposed to 32.5 µM ZDV. D – Cell exposed to 65 µM ZDV showing sticky chromosomes. E – Normal anaphase (early) from the negative control group. F – Mitotic figure from cell exposed to 6.5 µM ZDV showing anaphase bridges (arrowed). G – Mitotic figure showing cell exposed to 6.5 µM ZDV; arrows indicate uneven breaks (black) and chromosomal fragment (patterned). H – Interphase cells exposed to 6.5 µM ZDV indicating interphase arrest. *Challenges with instruments delayed taking micrographs till some slides started drying.</p

Root length during the 96(horizontal stripes) and 144 hr (vertical stripes) growth periods.

<p>For 96(NC  =  negative control), ZDV or NVP. From 96 hr to 144 hr (vertical stripes), all bulbs were grown in water without drug. Root length (mm) shown is mean ± Standard error, with n = 5 bulbs per group.</p

Number of Pregnancies obtained from the F₁ treatment groups.

<p>Number of Pregnancies obtained from the F₁ treatment groups.</p

Dominant lethal assay (DLA) after males were treated with Zidovudine or Nevirapine for four weeks.

<p>DLA simulates when the “father-only” is ARV treated.</p><p>EMS = Ethylmethylsulfonate (one-time dose); ZDV = Zidovudine; NVP = Nevirapine.</p>a<p>Number of pregnancies observed after 1∶1 mating.</p>b<p>Number of pregnancies before/after adding dams with heavy arterial linings to the pregnancy count. Dams with heavy arterial lining of the uterus and/or uterine fluids indicate fertile mating had occurred but was aborted early.</p>c<p>Number of implants per pregnant dam or the average from all pregnant dams in the group.</p><p>Statistical analysis could not be performed because of several missing values.</p><p>Dominant lethal assay (DLA) after males were treated with Zidovudine or Nevirapine for four weeks.</p